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Dissertations / Theses on the topic 'Gene Gata3'

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Published: 11 September 2021
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1

Gilli, Simone Cristina Olenscki. "Regulação do gene gata3 humano pelo virus HTLVI." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311958.

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Orientador: Sara T. O. Saad
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A infecção pelo vírus linfotrópico de células T tipo I (HTLV I) tem sido associada à leucemia/linfoma T do adulto (LLTA), à paraparesia espástica tropical! mielopatia associada ao HTLV I (PET/MAH), à uveíte e, recentemente, à Síndrome de Sjõgren e outras doenças do sistema conjuntivo. Os fatores que detenninam a evolução para essas doenças relacionadas à infecção são desconhecidos, mas podem estar ligados à predisposição genética e à resposta imune do hospedeiro. Camundongos com ausência do gene GATA3 demonstram várias e graves anormalidades morfológicas e fisiológicas no sistema nervoso central e periférico, além de comprometimento da hematopoese durante o desenvolvimento embrionário. Há, portanto, semelhanças entre os sistemas comprometidos na ausência do gene GATA3 e aqueles alterados secundariamente à infecção pelo HTLV I. Vários estudos sugerem que uma fosfoproteína viral presente no HTLVI, denominada Tax, ative a transcrição de vários genes envolvidos na produção de citocinas ou na resposta e na proliferação celular, como c-fos, c-myc, erg-I, IL-I, IL-2, GM-CSF. Entretanto, a crelação entre a infecção pelo vírus HTLV I e o fator de transcrição GATA3 ainda não havia sido determinada. Os objetivos do presente trabalho foram caracterizar a relação entre o fator de transcrição GATA3 e o vírus HTLV I, utilizando-se, para tanto, a técnica de RT-PCR semiquantitativo; analisar a relação entre o fator de transcrição GATA3 e o vírus HTLV I, por meio de estudos de interação DNA/proteína; e demonstrar, por estudos funcionais em modelos celulares in vitro, a resposta das regiões de controle transcricional do gene GATA3 à proteína Tax. Demonstramos, através do RT-PCR semi-quantitativo que ocorre uma evidente redução na expressão do gene GATA3 em portadores saudávies da infecção pelo HTLVI, e também de forma mais acentuada nos portadores de Leucemia Linfoma T do Adulto e Paraparesia Espástica Tropical/Mielopatia associada ao HTLVI. Estudos in vitro, que utilizaram construções com o gene reporter CAT direcionado pelo promotor e silenciador do gene GATA3 co-transfectados com vetores de expressão da proteína Tax e seu mutante, revelaram que Tax exerce atividade discreta no promotor de gene GATA3, mas reprime de modo marcante a atividade do promotor na presença de seu silenciador. Essa repressão provavelmente ocorre através da interação de tax com o fator de trans.crição ZEB, o silenciador do promotor do gene GATA3, uma vez que interação deste com a proteína Tax foi demonstrada no estudo de retardamento em gel. O estudo demonstrou, pela primeira vez, a regulação do gene GATA3 pelo vírus HTLVI. Essa regulação pode estar envolvida na fisiopatologia das doenças relacionadas à infecção pelo HTLVI
Abstract: The HTLV-I nonstructural protein Tax plays a crucial role in cellular transformation. It activates the transcription factors of various cellular genes and interacts with cellular proteins. Limited data are available on the interaction between specific T cell transcription factor GATA3 and Tax. hnplication for the significance ofGATA3 on T-cell development and function, (Th2) differentiation, and a role ofGATA3 during immune response has been reported. To determine the effect of the Tax protein on GATA3 gene expression, we investigated the interaction between this protein and the GATA3 promoter and repressor regions. The semi quantitative RT-PCR demonstrated a considerable decrease in the expression of the GATA 3 cDNA all subjects infected by HTLV I and no expression of GATA 3 mRNA was observed in one subject with ATLL and another with HAM/TSP. Results demonstrated an interaction between Tax and GATA3 gene and a role ofTax in the negative regulation of GATA3 expression, through its interaction with the repressor, ZEB. This interaction may be involved in the pathophysiology of adult T cell leukemiallymphoma and tropical spastic paraparesis/HTLV-I-associated myelophathy
Doutorado
Clinica Medica
Doutor em Clínica Médica
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2

Medeiros, Priscila [UNESP]. "Epidemiologia genética em hanseníase: estudo de associação do gene GATA3." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/140259.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundação Paulista Contra a Hanseníase
hanseníase é uma doença de caráter complexa causada pelo Mycobacterium leprae, que é um patógeno intracelular obrigatório com predileção por macrófagos na pele e células de Schwann nos nervos periféricos. O genoma altamente conservado do bacilo sugere que o patógeno não seja o responsável pela variedade de fenótipos clínicos e biológicos observada na doença, atribuindo grande importância aos fatores genéticos do hospedeiro. Estudos de ligação do tipo genome-wide apontaram um locus de susceptibilidade para a doença na região cromossômica 10p13 e o gene GATA3, localizado na região 10p15, é um forte candidato a fazer parte dessa associação devido à sua localização no genoma e ao seu papel na resposta imune. O GATA-3 é um fator de transcrição clássico na diferenciação de células Th2, no entanto, sabe-se hoje que essa proteína possui outras funções importantes para o sistema imune. Nós empregamos a estratégia de estudo de associação do tipo caso-controle em série, utilizando duas amostras populacionais do Brasil com 1.633 indivíduos, para testar sete variantes genéticas do GATA3. Um estudo funcional também foi conduzido para avaliar o efeito dos polimorfismos associados sobre a expressão de GATA-3 e produção de citocinas. O alelo A do polimorfismo rs10905284 foi associado com resistência para a hanseníase em ambas as amostras. Na análise combinando as duas amostras este efeito do alelo A foi confirmado (OR 0,67; IC95%: 0,54-0,84; p=0,0004). A análise funcional mostrou que os indivíduos portadores do genótipo AA expressam altos níveis da proteína GATA-3 nos linfócitos. Portanto, nós confirmamos que o marcador rs10905284 está associado à hanseníase na população brasileira e influencia os níveis de expressão do fator de transcrição GATA-3
Leprosy outcome is a complex trait and the host-pathogen-environment interaction defines the emergence of the disease. The causative agent of the disease, Mycobacterium leprae, exhibits a conserved genome and could not be accountable for the variety of outcomes observed from exposition, infection and disease. Thus, host genetic risk factors have been successfully associated to leprosy. The 10p13 chromosomal region was linked to leprosy in familial studies and the GATA3 gene is a strong candidate to be part of this association due to its locus and the role that exerts in the immune response. The GATA-3 is a transcription factor involved in the Th2 cell differentiation, however, today it is recognized the ample role of this protein in the immune response. Here, we applied a stepwise strategy to test genetic variants at GATA3 in two case-control samples from Brazil comprising a total of 1,633 individuals. A functional investigation was also conducted to evaluate the effect of the polymorphisms on the GATA-3 protein and the cytokines production. The A allele of rs10905284 marker was associated to leprosy resistance in both samples. In the analysis combining the two samples this effect was reinforced (OR 0,67; CI95%: 0,54-0,84; p=0,0004). The functional analysis showed that individuals carrying AA genotype express higher levels of GATA-3 protein in lymphocytes. So, we confirmed that the rs10905284 is a locus associated to leprosy in the Brazilian population and influences the levels of this transcription factor.
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3

Medeiros, Priscila. "Epidemiologia genética em hanseníase : estudo de associação do gene GATA3." Botucatu, 2015. http://hdl.handle.net/11449/140259.

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Orientador: Ana Carla Pereira Latini
Coorientador: Vânia Nieto Brito de Souza
Banca: Carlos Magno Castelo Branco Fortaleza
Banca: Milton Ozório Moraes
Resumo: hanseníase é uma doença de caráter complexa causada pelo Mycobacterium leprae, que é um patógeno intracelular obrigatório com predileção por macrófagos na pele e células de Schwann nos nervos periféricos. O genoma altamente conservado do bacilo sugere que o patógeno não seja o responsável pela variedade de fenótipos clínicos e biológicos observada na doença, atribuindo grande importância aos fatores genéticos do hospedeiro. Estudos de ligação do tipo genome-wide apontaram um locus de susceptibilidade para a doença na região cromossômica 10p13 e o gene GATA3, localizado na região 10p15, é um forte candidato a fazer parte dessa associação devido à sua localização no genoma e ao seu papel na resposta imune. O GATA-3 é um fator de transcrição clássico na diferenciação de células Th2, no entanto, sabe-se hoje que essa proteína possui outras funções importantes para o sistema imune. Nós empregamos a estratégia de estudo de associação do tipo caso-controle em série, utilizando duas amostras populacionais do Brasil com 1.633 indivíduos, para testar sete variantes genéticas do GATA3. Um estudo funcional também foi conduzido para avaliar o efeito dos polimorfismos associados sobre a expressão de GATA-3 e produção de citocinas. O alelo A do polimorfismo rs10905284 foi associado com resistência para a hanseníase em ambas as amostras. Na análise combinando as duas amostras este efeito do alelo A foi confirmado (OR 0,67; IC95%: 0,54-0,84; p=0,0004). A análise funcional mostrou que os indivíduos portadores do genótipo AA expressam altos níveis da proteína GATA-3 nos linfócitos. Portanto, nós confirmamos que o marcador rs10905284 está associado à hanseníase na população brasileira e influencia os níveis de expressão do fator de transcrição GATA-3
Abstract: Leprosy outcome is a complex trait and the host-pathogen-environment interaction defines the emergence of the disease. The causative agent of the disease, Mycobacterium leprae, exhibits a conserved genome and could not be accountable for the variety of outcomes observed from exposition, infection and disease. Thus, host genetic risk factors have been successfully associated to leprosy. The 10p13 chromosomal region was linked to leprosy in familial studies and the GATA3 gene is a strong candidate to be part of this association due to its locus and the role that exerts in the immune response. The GATA-3 is a transcription factor involved in the Th2 cell differentiation, however, today it is recognized the ample role of this protein in the immune response. Here, we applied a stepwise strategy to test genetic variants at GATA3 in two case-control samples from Brazil comprising a total of 1,633 individuals. A functional investigation was also conducted to evaluate the effect of the polymorphisms on the GATA-3 protein and the cytokines production. The A allele of rs10905284 marker was associated to leprosy resistance in both samples. In the analysis combining the two samples this effect was reinforced (OR 0,67; CI95%: 0,54-0,84; p=0,0004). The functional analysis showed that individuals carrying AA genotype express higher levels of GATA-3 protein in lymphocytes. So, we confirmed that the rs10905284 is a locus associated to leprosy in the Brazilian population and influences the levels of this transcription factor.
Mestre
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4

Gilmour, Jane. "The role of GATA3 and c-maf in human T-cell cytokine gene expression." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427926.

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5

Whyatt, David John. "Erythroid development and GATA-1." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239713.

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6

Tarradas, Pou Anna. "Els factors GATA4 i GATA5 en la regulació transcripcional del gen que codifica pel canal de sodi cardíac (SCN5A)." Doctoral thesis, Universitat de Girona, 2017. http://hdl.handle.net/10803/405732.

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The SCN5A gene encodes the alpha subunit of the cardiac sodium channel (NaV1.5), which is responsible for the influx of sodium ions through membrane of cardiomyocytes. Different evidences suggest that an aberrant expression of the SCN5A gene may cause cardiac arrhythmias. However, the mechanisms that control SCN5A expression regulation are largely unknown. This thesis proposes a new mechanism of SCN5A transcriptional regulation in the adult human heart: transcription factors GATA4 and GATA5 synergize in the activation of the SCN5A expression. In addition, it has been proposed that GATA4 activity on the SCN5A is regulated by acetylation/deacetylation via the acetyltransferase p300 and the deacetylase HDAC2. It has been identified three lysines of GATA4 that are targets of p300 and HDAC2. In summary, this study contributes to further understand the molecular basis of the cardiac arrhythmias associated with alteration of sodium currents
El gen SCN5A codifica per la subunitat alfa del canal de sodi cardíac dependent de voltatge (NaV1.5), el qual permet l’entrada de ions sodi a través de la membrana dels cardiomiòcits. Diverses evidències suggereixen que una expressió anòmala del gen SCN5A pot donar lloc a arítmies cardíaques. Malauradament, els mecanismes que regulen l’expressió d’SCN5A són molt poc coneguts. Aquesta tesi proposa un nou mecanisme de regulació transcripcional del gen SCN5A en el cor humà adult: els factors de transcripció GATA4 i GATA5 activen sinèrgicament l’expressió del gen SCN5A. També s’ha proposat que l’activitat de GATA4 sobre SCN5A està regulada per un mecanisme d’acetilació/desacetilació a on hi participen l’acetiltransferasa p300 i la desacetilasa HDAC2. S’han identificat tres residus de lisines de GATA4 que són dianes de p300 i HDAC2. En resum, aquest estudi permet entendre millor les bases moleculars de les arítmies cardíaques associades amb alteracions del corrent de sodi
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7

Borges, Gustavo. "Mutações no gene GATA2 em pacientes com síndromes de falência medular." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17154/tde-07062017-103827/.

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Citopenia é um importante sinal de falência medular, sendo um achado comum de várias doenças, dentre as quais se destacam as mielodisplasias e a anemia aplástica. As mielodisplasias correspondem a um grupo de alterações hematopoéticas de natureza clonal, cuja principal característica é a hematopoese ineficaz, clinicamente manifesta como uma medula óssea celular, porém associada a citopenias. Já a anemia aplástica apresenta uma medula hipo ou acelular sem evidência de infiltração neoplásica, sendo substituída por tecido gorduroso. O gene GATA2 é um fator regulador da hematopoese, atuando também na manutenção e proliferação do pool de células-tronco e progenitoras hematopoéticas. Recentemente, mutações constitucionais no gene GATA2 foram descritas na síndrome de monocitopenia e infecção micobacteriana (MonoMac), que eventualmente cursa com outras citopenias, medula hipocelular ou mesmo mielodisplasia. Entretanto, a contribuição de mutações no gene GATA2 para o desenvolvimento de anemia aplástica adquirida e síndrome mielodisplásica não é conhecida. Neste trabalho, propomos pesquisar mutações no gene GATA2 em pacientes com anemia aplástica adquirida e síndrome mielodisplásica, por meio de sequenciamento direto do DNA. Adicionalmente, também avaliaremos as subpopulações linfocitárias no sangue periférico e níveis de citocinas plasmáticas no intuito de correlacionar a presença de mutação do GATA2 a um perfil imunológico.
Cytopenia is an important signal of marrow failure, being commom to various diseases, among them myelodysplasia and aplastic anemia. Myelodysplasia is a group of hematopoietic clonal disorders, with inneficient hematopoiesis, cellular bone marrow with associated cytopenias. The aplastic anemia presents a hypo or even acellular bone marrow without any evidence of neoplastic infiltration with the stem cells being substituted by fat. The GATA2 gene is a key regulator of hematopoiesis, also acting on the maintenance and proliferation of stem and progenitor cells. Recently, constitutional mutations in the GATA2 gene were described in MonoMAC syndrome, which eventually presents cytopenias, hypocellular marrow or even myelodysplasia. However, the contribution of GATA2 mutations for the development of acquired aplastic anemia or myelodysplasia is not known. In this work we aim to search for GATA2 gene mutations in patients with acquired aplastic anemia and myelodysplasia through Sanger sequencing. Also, we will evaluate the levels of subpopulations of lymphocytes and the plasmatic levels of cytokines to establish a correlation between the presence of mutation in the GATA2 and a specific immune profile
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Lee, Pei Yun Bronner-Fraser Marianne. "Function and regulation of the Strongylocentrotus purpuratus gatae gene /." Diss., Pasadena, Calif. : California Institute of Technology, 2007. http://resolver.caltech.edu/CaltechETD:etd-04072007-221302.

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Pregernig, Gabriela. "Determinants of GATA1-mediated gene regulation during erythroid maturation." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/112505.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2017.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 151-171).
Hematopoiesis has long been used as a model system to study development and lineage decision-making. Within this branch of development, erythropoiesis is the process through which mature red blood cells arise from progenitor cells. In this context, GATA1 is widely considered to be the master transcription factor for erythropoiesis, controlling the expression of a vast majority of the genes involved in red blood cell maturation. GATA1 dysfunction has been shown to cause several human disorders, including anemias and thalassemias, and has been linked to the onset of various types of leukemia. GATA1 has been shown to function as both a gene activator and repressor, posing the question of how it distinguishes between various categories of genes and regulates them. In this thesis, we apply a combination of systems and molecular biology approaches in order to gain a better understanding of various regulatory mechanisms centered around GATA1. In the main study of this thesis, we uncover a new physical interaction between GATA1 and the cohesin complex, which has previously been involved in establishing three-dimensional chromatin architecture in the nucleus. We collected chromatin interaction data in a murine cell line model for erythropoiesis, and identified tens of thousands of DNA looping events in both progenitor and differentiated cells. Integration of these chromatin interaction maps with gene expression and transcription factor occupancy datasets revealed new principles underlying gene regulation, and suggests that GATA1 plays a major role in orchestrating the 3D organization of the differentiating erythroid cell. In a second study, we identify a new feedback mechanism which facilitates the replacement of GATA2, a transcription factor expressed at earlier stages of hematopoiesis, by GATA1. We show that Fbw7, an ubiquitin ligase protein trans-activated by GATA1, targets GATA2 for proteosomal degradation, thus reducing its halflife and leading to more efficient GATA factor switching. Finally, in a last section, we characterize the GATA1 -interacting transcription factors zfp281 and zfp148, and show that they play functionally redundant roles in erythroid development. Altogether, this thesis presents new insights into GATA1 various aspects of GATA1 biology, which will contribute to our understanding of mechanisms of gene regulation.
by Gabriela Pregernig.
Ph. D.
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Gillis, William Joseph. "The evolution of metazoan GATA transcription factors /." Connect to title online (Scholars' Bank) Connect to title online (ProQuest), 2008. http://hdl.handle.net/1794/8568.

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Thesis (Ph. D.)--University of Oregon, 2008.
Typescript. Includes vita and abstract. "This dissertation includes both ... previously published and unpublished co-authored material"--P. v. Includes bibliographical references (leaves 120-135). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.
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Hollanda, Luciana Maria de. "Funções do gene GATA1 : contribuições do estudo de mutações em doenças hematologicas." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316736.

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Orientador: Fernando Ferreira Costa
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Várias mutações hereditárias no gene GATA1 localizadas no éxon 4 e conseqüentemente que afetam o domínio dedo de zinco N-terminal foram descritas em algumas famílias que apresentavam graus variáveis de plaquetopenia com ou sem anemia. Por outro lado, mutações adquiridas no éxon 2 deste gene foram observadas em quase todos os casos estudados de pacientes com Síndrome de Down e que apresentavam TMD ou AMKL. Essas mutações impedem a síntese da proteína total, mas permite a síntese da isoforma menor da proteína, denominada GATA-1s. Experimentos em camundongo sugeriram que a síntese única da isoforma GATA-1s seria suficiente para induzir hemopoese normal nesses animais. Neste trabalho descrevemos em pacientes e portadores de uma família a mutação 332G--C localizada no éxon 2 do gene GATA 1 que conduz a produção apenas da proteína GATA-1s nos homens afetados. Os perfis hematológicos desses pacientes demonstraram anemia macrocítica, neutropenia em vários casos e número normal de plaquetas. Em seu conjunto, esses dados sugerem que a proteína GATA -1s, produzida em níveis normais ou baixos não é suficiente para conduzir à eritropoese normal. Além disso, este é o primeiro estudo onde uma mutação hereditária no éxon 2 do gene GATA1 origina apenas a proteína GATA-1s e não provoca AMKL ou TMD em indivíduos não portadores de síndrome de Down. Desta forma este estudo indica que outros eventos cooperativos, como outras mutações ou a trissomia do cromossomo 21 provavelmente podem ser os responsáveis por essas anomalias em crianças com síndrome de Down
Abstract: Inherited mutations in exon 4 of the GATA1 gene, which codes for the N-terminal zinc finger domain of GATA-1, have been found in some families, leading to a familial dyserythropoietic anemia with thrombocytopenia, X-linked thrombocytopenia and X-linked thalassemia with thrombocytopenia. Acquired somatic mutations in exon 2 of the hematopoietic transcription factor GATA-1 have been found in individuals with Down syndrome with both transient myeloproliferative disorder and acute megakaryoblastic leukemia . These mutations prevent the synthesis of the full-length protein but allow the synthesis of its short isoform, GATA-1s. Experiments in mice suggest that GATA-1s supports normal adult megakaryopoiesis, platelet formation and erythropoiesis. Here we report a mutation, 332G-C, in exon 2 of GATA1, leading to the synthesis of only the short isoform in seven affected males from two generations of a family. Hematological profiles of affected males demonstrate macrocytic anemia, normal platelet counts and neutropenia in most cases. Altogether, data suggest that GATA-1s alone, produced in low or normal levels, is not sufficient to support normal erythropoiesis. Moreover, this is the first study to indicate that a germline splicing mutation does not lead to leukemia in the absence of other cooperating events, such as Down syndrome
Doutorado
Genetica Animal e Evolução
Doutor em Genetica e Biologia Molecular
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Eisbacher, Michael School of Medical Science UNSW. "The regulation of megakaryocyte-specific genes by Fli-1 and GATA-1." Awarded by:University of New South Wales. School of Medical Science, 2003. http://handle.unsw.edu.au/1959.4/19171.

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The successive activation of tissue-specific genes during cellular differentiation is orchestrated by the formation of transcriptional complexes consisting of cellspecific and ubiquitous transcription factors. Understanding the molecular events associated with normal megakaryocyte (Mk) differentiation is an issue of central importance to haematology. The aims of this study were therefore to: (i) define the transcription factors responsible for regulating the expression of Mkspecific genes such as Glycoprotein IX, (ii) identify the protein partners of such important Mk-regulatory transcription factors and (iii) examine the mechanisms utilised by these factors to regulate gene expression. First, the regulatory elements in the GPIX promoter required for basal and inducible expression were examined in megakaryoblastic Dami cells stimulated to undergo differentiation. The resulting data suggested that an Ets site in the GPIX promoter binding the Ets-family member Fli-1 was crucial in regulating both constitutive and inducible GPIX expression. Second, a two-hybrid screen of a K-562 cDNA library was used to identify transcription factors that interacted with Fli-1 and were potential regulators of Mk development. Results of this screen identified a novel protein-protein interaction with GATA-1, a previously well-characterised zinc finger transcription factor also implicated in erythroid and Mk development. Mapping of the domains required for the interaction show that the zinc fingers of GATA-1 interact with the Ets domain of Fli-1. The biological significance of the Fli-1/GATA-1 interaction was demonstrated in transient transfection assays, which resulted in synergistic activation of Mkspecific promoters. Analysis of Fli-1 and GATA-1 expression in a series of erythroleukaemic and megakaryoblastic cell lines demonstrated that the Fli- 1/GATA-1 combination correlates with a Mk-phenotype. Moreover, expression of Fli-1 in K-562 cells (a line rich in GATA-1 but normally lacking Fli-1) induces endogenous GPIX expression. Quantitative mobility shift assays reveal that Fli- 1 and GATA-1 exhibit cooperative DNA-binding in which the binding of GATA-1 to DNA is increased approximately 26 fold in the presence of Fli-1. This data provides a mechanism for the observed transcriptional synergy. In conclusion, this work suggests that Fli-1 and GATA-1 work together through protein-protein interaction and cooperative DNA-binding to activate the expression of genes associated with the terminal differentiation of Mks.
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Peters, David G. "Characterisation of GATA binding proteins using Aspergillus nidulans as a model organism." Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240865.

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Conlon, Helen Elizabeth. "The characterization of 'areB', encoding a novel GATA factor of 'A. nidulans'." Thesis, University of Liverpool, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272780.

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Oikonomopoulos, Spyridon. "Inferring structural properties of protein-DNA binding using high-throughput sequencing : the paradigm of GATA1, KLF1 and their complexes GATA1/FOG1 and GATA1/KLF1 : insights into the transcriptional regulation of the erythroid cell lineage." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:72b92906-4ef6-4c1d-9155-484521027e2e.

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GATA1 and KLF1 are transcription factors that regulate genes which are important for the development of erythroid cells. The GATA1 transcriptional co-factor FOG1 has been shown to be essential in a wide range of GATA1 dependent cellular functions. Here we tried to understand the diverse mechanisms by which GATA1 and KLF1 recognize their binding sites, how the GATA1 recognition mechanisms are affected by complexation with either FOG1 or KLF1 and how the GATA1 recognition mechanisms affect the transcriptional regulation of the erythroid differentiation. We profiled the DNA binding specificities/affinities of a GATA1 fragment (mGATA1NC), that contains only the two DNA binding domains (N-terminal and C-terminal Zn finger), and the DNA binding specificities/affinities of a KLF1 fragment (mKLF1257-358), that contains the three DNA binding domains, using a novel methodology that combines EMSA with high throughput sequencing (EMSA-seq (Wong et al., 2011a)). We also profiled the DNA binding specificities of the C-terminal Zn finger of GATA1 alone (mGATA1C), the wt-mGATA1, the wt-mGATA1/wt-mFOG1 complex and the mGATA1NC/mKLF1257-358 complex. At first, we confirmed that the N-terminal Zn finger of GATA1 has a strong preference for the “GATC” motif, whereas the C-terminal Zn finger of GATA1 has a strong preference for the “GATA” motif. Next, we found that in the mGATA1NC, both DNA binding domains can bind simultaneously a wide range of different positional combinations of the co-occurring “GATA” and “GATC” motifs, on the same DNA sequence. The wt-mGATA1 did not show the ability to bind in the same co-occurring motifs implying an effect of the non-DNA binding domains of the protein in the regulation of its DNA binding specificities. On the contrary, complexation of wt-mGATA1 with the wt-mFOG1 partially restored its ability to bind in a now limited range of different positional combinations of the co-occurring “GATA” and “GATC” motifs, on the same DNA sequence. Similar observations were made for other pairs of GATA1 N-terminal and C-terminal Zn finger specific motifs. We then projected the GATA1 DNA binding specificities/affinities in vivo and we classified the GATA1 ChIP-seq peaks in low, medium or high affinity based on the number of the GATA1 motifs. We noticed that high affinity GATA1 ChIP-seq peaks tend to appear in regions with low nucleosome occupancy. We also noticed that GATA1 ChIP-seq peaks in the enhancer regions are usually high affinity whereas GATA1 ChIP-seq peaks in the proximal promoter regions are usually low affinity. Additionally, we observed that high affinity GATA1 ChIP-seq peaks are usually found in regions with increased levels of H3K4me2 and are associated with a higher decrease in the H3K4me3 levels on the TSS of the nearby genes. None of these GATA1 related in vivo observations were found for the KLF1 ChIP-seq positions. These findings significantly advance our understanding of the DNA binding properties of GATA1, KLF1 and their complexes and give an insight on the importance of the GATA1 DNA binding affinities in the regulation of the erythroid transcriptional program. Overall the work establishes an experimental and analytical framework to investigate how transcriptional co-factors can change the DNA binding specificities of specific transcription factors and how integration of the transcription factor DNA binding affinities with in vivo data can give novel insights into the transcriptional regulation.
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Wang, Ling. "GATA-4 mediated upregulation of Kv 4.2 gene expression in mouse heart." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0016/MQ49662.pdf.

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Lahlil, Rachid. "Facteurs de transcription et differenciation erythroide de la lignee leucemique humaine k562 : modulation de gata-1, gata-2 et nf-e2 par un inhibiteur (azt) ou par une strategie sens et antisens." Reims, 1997. http://www.theses.fr/1997REIMP206.

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18

Montagni, Elisa 1984. "Transcription factor GATA6 and ISC gene SMOC2 in the regulation of BMP pathway in intestinal adenoma." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/523489.

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The first chapter identifies the transcription factor GATA6 as negative regulator of a transcriptional circuit dedicated to prevent the expansion of Adenoma Stem Cells (AdSCs) during the onset of colorectal cancer (CRC). In particular, we show that GATA6 directly activates the expression of the WNT pathway component LGR5 and represses BMP levels in adenoma by competing with the β-catenin/TCF4 complex for the binding to BMP4 enhancer regions. As a result of this mechanism, two compartments are established within an adenoma: a BMP positive differentiated cell zone and a BMP negative undifferentiated cell zone, where AdSCs reside. Genetic deletion of Gata6 increases BMP levels in the AdSC compartment, inhibiting self-renewal and intestinal tumorigenesis. These findings represent a key contribution to understand the mechanisms that regulate tumor hierarchy and reveal for the first time the existence of a niche that protects AdSCs from BMP signals. The second chapter focuses on the functional characterization of Smoc2, a novel Intestinal Stem Cell (ISC) gene. We generated genetic mouse models in order to overexpress or ablate Smoc2 in the intestine. We found that SMOC2 acts as a BMP inhibitor in the intestine and that it is not only restricted to epithelial Stem Cells (SCs) but it is also expressed by the stroma. Although it is dispensable for normal ISC maintenance and intestinal homeostasis, high levels of SMOC2 are required for tumorigenesis. Indeed, Smoc2 overexpression leads to spontaneous development of hamartomas and enhances adenoma formation in mice with an Apc mutant background; inversely, Smoc2 deficiency decreases tumorigenesis and prolongs survival of Apc mutant mice. In particular, we observed that SMOC2-mediated BMP inhibition positively affects Insulin-like Growth Factor (Igf1) expression in adenoma endothelial cells (ECs). Our data suggest that SMOC2 could enhance tumor-associated inflammation through BMP-mediated Igf1 regulation in the stroma.
El primer capítulo describe la identificación del factor de transcripción GATA6 como regulador negativo de un circuito transcripcional fisiológico dedicado a reprimir la expansión de las células madre de los adenomas (Adenoma Stem Cells o AdSCs) en el inicio de la tumorogénesis colorrectal. De manera específica, mostramos como el factor GATA6 activa directamente la expresión del componente de la ruta de WNT, LGR5, y también directamente reprime niveles de hormona BMP (Bone Morphogenetic Protein) a través de la competición directa con el complejo beta-catenina-TCF4 por la unión a regiones enhancer del gen BMP4. Como resultado de este circuito transcripcional que hemos descubierto, en los adenomas se generan dos compartimentos, una zona positiva para la señalización mediada por BMP que contiene las células diferenciadas de los adenomas, y un área negativa para BMP, donde residen y se expanden las AdSCs. La ablación genética de Gata6 incrementa los niveles de BMPs en el compartimento de las AdSCs, inhibiendo la autorenovación de las mismas y por ende la tumorogénesis. Este descubrimiento representa una aportación clave para entender los mecanismos que regulan la jerarquía tumoral y revelan por primera vez la existencia de un nicho que protege las AdSCs de las señales de BMP. El segundo capítulo describe la caracterización funcional de Smoc2, uno de los genes identificados en el laboratorio dentro del programa genético específico de las células madre del intestino (Intestinal Stem Cells o ISCs). Durante el transcurso de la tesis
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19

Klockziem, Matti [Verfasser]. "Regulation des GATA4 Gens durch den Wilmstumor-Transkriptionsfaktor WT1 / Matti Klockziem." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1176635549/34.

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20

Krueger, Katherine C. "Transcriptional Regulation of FEV, a Human Serotonin Neuron Developmental Control Gene." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1231289529.

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21

Dellow, Kimberley Anne. "Identification and characterisation of factors binding the human cardiac troponin I gene promoter." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312168.

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22

Klejevskaja, Beata. "Biophysical and functional studies of potential G-quadruplex motifs from the proximal GATA4 gene promoter." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/44979.

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GATA4 is well known as a cardiac transcription factor and recently has also been implicated in several cancers. Therefore, a fundamental understanding of its gene regulation is currently of high interest. It has been suggested that guanine-rich motifs found in gene promoters could potentially adopt a G-quadruplex DNA structure and play a role in regulating gene expression. Two conserved-potential G-quadruplex motifs were identified in the human and mouse proximal GATA4 promoter region and it was hypothesised that they could be involved in regulation of GATA4 expression. The biophysical characterisation of the identified G-quadruplex motifs showed that the motif-1 found 72bp downstream from the transcription start site (TSS) adopts a stable G-quadruplex structure, whereas the motif-2 located 10 bp downstream from the TSS folds predominantly into a hairpin structure. To evaluate the functional potential of G-quadruplex structure formation in the proximal GATA4 promoter, the GATA4 promoter was cloned onto a luciferase expression vector and a series of G-quadruplex mutants was generated. Mutations of motif-1 or motif-2 -quadruplex had no significant effect on GATA4 promoter activity. Despite this, GATA4 G-quadruplex structure-stabilising ligands, such as pyridostatin and TMPyP4, were found to down-regulate GATA4 promoter activity, likely due to off-target effects. To more closely resemble the quadruplex environment in gene promoters, G-quadruplex formation within DNA mini-circles was investigated by single-molecule FRET. DNA mini-circles were found to be a promising novel tool for biophysical characterisation of G-quadruplexes from gene promoters, as well as for studies of G-quadruplex interaction with ligands. This work presents evidence that not all G-quadruplex motifs found in gene promoters are biologically relevant. It was also found that commonly used G-quadruplex ligands can affect promoter activity mediated via alternative mechanisms to G-quadruplex. Finally, the feasibility of studying G-quadruplex structures embedded within mini-circle DNA was demonstrated.
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23

LIU, CONG. "REGULATION OF LUNG EPITHELIAL DIFFERENTIATION ALVEOLARIZATION AND GENE EXPRESSION BY GATA-6 IN VITRO AND IN VIVO." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026498687.

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24

Francius, Cédric. "ETUDE FONCTIONNELLE DU GENE GATA2 AU COURS DE LA NEUROGENESE DANS LA MOELLE EPINIERE VENTRALE EMBRYONNAIRE." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2007. http://tel.archives-ouvertes.fr/tel-00184253.

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Notre projet porte sur l'étude fonctionnelle du facteur de transcription GATA2 qui contrôle la mise en place de certaines populations neuronales. Mon travail de thèse est basé sur l'étude de sa fonction dans la moelle épinière.
Dans la moelle épinière ventrale embryonnaire, les motoneurones et 4 classes d'interneurones V0, V1, V2 et V3 sont générés dans des territoires distincts. Les V2 sont spécifiés dans un territoire adjacent à celui des motoneurones et sont subdivisés en V2a et V2b. Notre but est de déterminer le rôle de Gata2 durant la spécification des V2 et son l'influence sur la prolifération des progéniteurs neuraux.
Par une approche de perte et gain de fonction, nous avons montré que :
1. Gata2 inhibe la prolifération des progéniteurs neuraux avec un effet cellulaire-non autonome, en induisant un inhibiteur du cycle et en réprimant la voie Notch. Ce contrôle peut être découplé de la différenciation neuronale et ne nécessite pas d'activité proneurale.
2. Gata2 joue favorise l'émergence des V2 et réprime la différenciation des motoneurones, par la modulation des voies Shh et TGF-Β. Gata2 participe à la dichotomie des V2 car il favorise la différenciation des V2b et inhibe celle des V2a. Nous avons montré que les V2a sont glutamatergiques et les V2b sont GABAergiques.
Cette étude a mis en évidence la complexité des mécanismes moléculaires à l'origine de la diversité neuronale.
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25

Llewellyn, Katrina. "The role of an A-form DNA element in transcriptional regulation of the Xenopus gata2 gene." Thesis, University of Portsmouth, 2008. https://researchportal.port.ac.uk/portal/en/theses/the-role-of-an-aform-dna-element-in-transcriptional-regulation-of-the-xenopus-gata2-gene(a8eaf58a-9c01-400e-9ad0-2bd1a9cb5884).html.

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The development of a single celled embryo to a fully developed organism is tightly controlled by gene expression. Different genes are temporally and spatially regulated to form different cell types. Genes regulate each other to produce products that give rise to distinct cell fates and these interactions are referred to as gene regulatory networks (GRNs). Haematopoiesis is modulated by a complex GRN and one critical factor in this developmental pathway is GA TA2. Gata2 is a transcription factor and when it is inactivated in mice no erythrocytes develop. Xenopus laevis gata2 expression is itself regulated by another transcription factor, CCAA T box transcription factor (CBTF). CBTF is a multi-protein complex and one subunit in particular has been shown to be critical for gala2 activation, ilf3. Xenopus laevis ilf3 contains two double stranded RNA-binding domains (dsRBDs) that are necessary for its DNA binding and transcriptional activity. Binding to DNA is unusual for dsRBDs. It has been hypothesised that the ilf3 dsRBDs can bind the gata2 promoter and activate transcription only because binding is mediated by the partial A-form structure of the gata2 promoter, which mimics dsRNA. This hypothesis was tested by altering the degree of A-form structure in the promoter, then measuring binding of CBTF and transcriptional activation of gata2. Data presented in this thesis show that A-form structure is important for binding of CBTF and transcriptional activation at the gata2 promoter; however the presence of the inverted CCAA T box is an absolute requirement. In the absence of the inverted CCAA T box a strongly A-form sequence is not sufficient for activity. Secondly, the promoter region used in these experiments was shown to give correct temporal expression but not spatial. Suggesting a region(s) elsewhere directs correct spatial expression. Finally, the residues of ilf3 critical for dsRNA binding were examined to see if they were also critical for DNA binding. Those residues involved in binding dsRNA are almost all involved in binding DNA, although one mutant (K455A) reduced dsRNA binding but had no effect on DNA binding.
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26

Tan, Yu Yin Nicole Medical Sciences Faculty of Medicine UNSW. "Gene expression during activation of smooth muscle cells." Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43615.

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Cardiovascular disease, which involves the cardiac, cerebrovascular and peripheral vascular system, is the major cause of morbidity and mortality in the western world. Changes in the vascular microenvironment trigger cascades of molecular events involving altered signaling, transcription and translation of a gene. The aim of this thesis was to increase our understanding on the molecular regulation of activated vascular smooth muscle cells. The first study looking at PDGF-D expression provides new insights into the regulatory mechanisms controlling the phosphorylation of Sp1. Studies performed identified three amino acids in Sp1 (Thr668, Ser670 and Thr681) that is phosphorylated by PKC-zeta activated by AngII. In the second study, the translational regulatory role of a novel gene YrdC induced by injury was investigated. Current knowledge of translational regulators controlling altered gene expression is little and studies in this thesis shows a splice variant of YrdC playing an important role in controlling mRNA translation and thus protein synthesis in the context of injury. The final study investigated in this study was the increased expression of the apoptotic FasL by the activation of GATA6. Although FasL has been extensively studied over the years, this is the first study linking a GATA factor with FasL in any cell type and provides key insights into the transcriptional events underpinning FasL-dependent SMC apoptosis following exposure to AngII.
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Rogers, David. "CIS-REGULATORY ANALYSIS OF THE PIGMENT CELL DIFFERENTIATION GENE POLYKETIDE SYNTHASE." Master's thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/2701.

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The analysis of Gene Regulatory Networks (GRNs) is essential to understanding the complete process of embryo development. Elucidating every gene regulatory circuit from maternal regulatory inputs all the way to the activation of differentiation gene batteries is an important step in increasing our understanding of developmental biology. In this work I study the cis-regulatory architecture of a pigment cell differentiation gene, polyketide synthase (SpPks) in the sea urchin Strongylocentrotus purpuratus. SpPks encodes an enzyme that is responsible for the biosynthesis of the sea urchin pigment echinochrome in larval pigment cells. The analysis of the promoter of a differentiation gene will lead to identifying the direct upstream regulators and ultimately to elucidating the structure of the upstream gene regulatory network, which is mostly uncharacterized. From previous studies the transcription factors SpGcm and SpGatae are predicted to be positive regulators of SpPks. Here, I identify a minimal 1kb promoter region containing putative DNA-binding sites for both GCM and GATAE that is able to recapitulate the expression of SpPks. I further show by mutagenesis that a putative DNA-binding site for GCM located 1,179 base pairs upstream of the start of transcription is a direct target for the positive cis-regulation of SpPks. Quantitative analysis of the transcriptional regulatory function of the GCM-mutagenized construct suggests that GCM is not necessary for the start of SpPks transcription but is required for its maintenance. Several GATA E binding sites have been identified within the minimal promoter for SpPks by means of consensus sequence. My analysis suggests that GATA E may be a direct positive regulator and could potentially be required for the onset of transcription of SpPks, though further experimentation will be necessary to characterize the exact regulatory function of GATA E.
M.S.
Department of Biology
Sciences
Biology MS
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28

Ronsmans, Aria. "Mechanisms of nitrogen catabolite repression-sensitive gene regulation by the GATA transcription factors in Saccharomyces cerevisiae." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209169.

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The process of specific gene transcription by RNA polymerase II (Pol II) is initiated by the

binding of specific transcription factors to DNA. A global understanding of the mechanisms of gene

transcriptional regulation of Saccharomyces cerevisiae goes through the description of the targets and

the behavior of those transcription factors.

The GATA factors are specific transcription factors intervening in the regulation of Nitrogen

Catabolite Repression (NCR)-sensitive genes, a mechanism encompassing the transcriptional

regulations leading to the preferential use of good nitrogen sources of the growth medium of yeast in

the presence of less good nitrogen sources. Those 4 GATA factors involved in NCR comprise 2

activators (Gat1 and Gln3) and 2 repressors (Gzf3 and Dal80).

Generally speaking, the promoters of genes have always been described like the main place for

the integration of the transcription regulation signals relayed by the general and specific transcription

factors and the chromatin remodeling factors. Furthermore, the GATA factors have been described as

integrating the external signals of nitrogen availability thanks to their specific DNA binding to

consensus GATA sequences in the promoter of NCR-sensitive genes. The results presented here

introduce many nuances to the model, notably implying new proteins but also new regions in the

regulation process of the NCR-sensitive gene regulation. Indeed, the first goal of this work is to

discover and understand the mechanisms of NCR-sensitive gene regulation that will explain the

variations in their expression levels in the presence of various nitrogen sources and their dependency

towards the GATA factors.

Strikingly, it appeared that GATA factor positioning was not limited to the promoter, but

occurred also in the transcribed region. It seems that the transcription factors may have been driven

by the general transcription machinery (Pol II). The binding of a chromatin remodeling complex, RSC,

has also been demonstrated in the coding region of NCR-sensitive genes. Moreover, the binding of the

histone acetyltransferase complex, SAGA, recruited by the GATA activators, was highlighted along

NCR-sensitive genes. The SAGA complex was also implied in their transcriptional regulation.

Finally, a ChIP-sequencing experiment revealed an unsuspected number and diversification of

targets of the GATA factors in yeast, which were not limited to NCR-sensitive genes.


Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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Chung, Pui-kei. "Heat shock cognate 70(HSC70)and gata transcription factor as the regulators of vitellogenesis in the shrimp Metapenaeus ensis." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B34835167.

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30

Kakita, Tsuyoshi. "p300 protein as a coactivator of GATA-5 in the transcription of cardiac-restricted atrial natriuretic factor gene." Kyoto University, 2001. http://hdl.handle.net/2433/150538.

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31

Chung, Pui-kei, and 鍾沛基. "Heat shock cognate 70(HSC70)and gata transcription factor as the regulators of vitellogenesis in the shrimp Metapenaeus ensis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B34835167.

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32

Wallach, Iwona. "Transkriptionelle Regulation des Erythropoietin-Rezeptor-Gens im zentralen Nervensystem." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15685.

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Derzeit wird die Anwendung von Erythropoietin (Epo) zur Neuroprotektion in präklinischen und klinischen Studien intensiv untersucht. Für die Neuroprotektion ist die Regulation des Erythropoietin-Rezeptors (EpoR) in neuronalen Zellen von hoher Relevanz. In dieser Arbeit wurden die transkriptionellen Mechanismen der EpoR-Regulation in humanen Neuroblastom-Zellen SH-SY5Y mit neuronalem Phänotyp untersucht. Da der hämatopoietische Transkriptionsfaktor GATA-1 die EpoR-Transkription in erythroiden Vorläuferzellen in Kooperation mit Sp1 stimuliert, wurde die Rolle der in neuronalen Vorläuferzellen exprimierten GATA-Transkriptionsfaktoren bei der EpoR-Expression untersucht. Es wurde eine in vitro Bindung von GATA-2, -3 und -4 an zwei Motive in der EpoR 5’-flankierenden Region (-274/-271; -47/-44) nachgewiesen. In Reportergen-Assays zeigten diese Genabschnitte eine bis zu 4,8-fache Aktivitätssteigerung bei Überexpression von GATA-2, -3 oder -4. Die endogene EpoR mRNA-Expression wurde dadurch aber nicht erhöht. Hypoxie (2% O2, 3 d) erhöhte die EpoR-Expression signifikant (1,8-fach, p < 0,01), wobei überexprimierte GATA-Transkriptionsfaktoren diesen Effekt nicht weiter steigerten. Die Gabe von Epo (5 U/ml, 3 d) hatte weder unter Normoxie noch unter Hypoxie einen Einfluss auf die EpoR-Expression. Die Promotoraktivität der Reporterkonstrukte wurde durch Mutation der GATA-Bindungsstellen nicht verändert, jedoch bei mutierter Sp1-Bindungsstelle inhibiert. Ein Fragment der 5’-flankierenden Region (-449/-285), das ein Cluster von Bindungsstellen für unterschiedliche Transkriptionsfaktoren enthält, zeigte die stärkste Promotoraktivität und rekrutierte offenbar die RNA-Polymerase II. In unserem Modell spielen die GATA-Faktoren keine direkte Rolle für die EpoR-Genregulation in neuronalen Vorläuferzellen. Die EpoR mRNA-Expression wird eher durch einen Komplex aus verschiedenen Transkriptionsfaktoren reguliert, der an eine 5’ des minimalen Promotors liegende DNA-Region zu binden scheint.
Since the use of erythropoietin (Epo) as neuroprotective agent is currently intensively studied in preclinical and clinical trials, regulatory mechanisms of the erythropoietin receptor (EpoR) in neuronal cells are of particular interest. In this study, the transcriptional mechanisms of EpoR regulation were analyzed in human neuroblastoma-derived SH-SY5Y cells, which exhibit a neuronal phenotype. Considering that the hematopoietic transcription factor GATA-1 stimulates EpoR transcription in cooperation with Sp1 in erythroid progenitors, the role of other GATA family members expressed in neuronal precursor cells were studied. In vitro, GATA-2, -3 and -4 were found to bind to two consensus motifs within the EpoR 5’-flanking region (-274/-271 and -47/-44). In reporter gene assays, these regions showed an up to 4.8-fold induction if GATA-2, -3 or -4 were overexpressed. However, forced expression of GATA-2, -3 and -4 did not enhance endogenous EpoR mRNA expression. Under hypoxia (2% O2, 3 d), EpoR expression was significantly upregulated in SH-SY5Y cells (1.8-fold, p < 0.01), but not further increased by the additional overexpression of the GATA factors. Incubation of the SH-SY5Y cells with recombinant Epo (5 U/ml, 3 d) had no effect on the EpoR expression under normoxia or hypoxia. The promoter activities of the reporter constructs were not changed by mutations in the GATA sites, but abolished by mutations of Sp1 binding sites. A fragment (-449/-285) of the 5’-flanking region that contains a cluster of binding sites for various transcription factors showed strongest promoter activity and was obviously directing the recruitment of RNA polymerase II. We conclude that GATA factors do not play a major role in regulating EpoR expression in our model for neuronal precursor cells. EpoR mRNA expression is rather regulated by a complex of various transcription factors, which may bind to a region upstream of the minimal promoter.
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Wada, Hiromichi. "A p300 as a coactivator of GATA-6 in the transcription of the smooth muscle-myosin heavy chain gene." Kyoto University, 2002. http://hdl.handle.net/2433/149677.

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34

Mehmet, Mugayer Boral. "Etablierung molekulargenetischer Methoden zur Mutationsanalyse des TBX1-Gens unter Verwendung der denaturierenden Hochdruck-Flüssigkeits-chromatographie (DHPLC)." Doctoral thesis, Universitätsbibliothek Leipzig, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-88720.

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Mit dem Ziel, die denaturierende Hochdruck-Flüssigkeitschromatographie (DHPLC) als standardisierte Methode in der molekulargenetischen Diagnostik des TBX1-Gens einzuführen, wurde an 35 Patienten mit begründetem klinischen Verdacht oder Nachweis eines congenitalen Herzfehlers die Mutationsanalyse etabliert und durchgeführt. Die erzielten Ergebnisse bestätigten die kosteneffiziente und zugleich einfache Durchführung des Verfahrens. In der Evaluation wurde für die DHPLC zudem eine hohe Sensitivität und Spezifität nachgewiesen, womit der zukünftige Einsatz dieser Methode im routinemäßigen Mutationsscreening gerechtfertig ist. Mittels DHPLC konnten im Rahmen der vorliegenden Dissertation insgesamt 14 verschiedene Veränderungen im TBX1-Gen identifiziert und in der anschließenden Sequenzanalyse als Polymorphismen (Normvarianten) charakterisiert werden.
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Morimoto, Tatsuya. "GATA-5 Is Involved in Leukemia Inhibitory Factor-Responsive Transcription of the β-Myosin Heavy Chain Gene in Cardiac Myocytes." Kyoto University, 2000. http://hdl.handle.net/2433/180844.

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36

DEVEAUX, SOPHIE. "Regulation des genes specifiques des megacaryocytes : role des facteurs de transcription gata, ets et nf-e2." Paris 6, 1998. http://www.theses.fr/1998PA066462.

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Notre equipe travaille sur la regulation de genes exprimes dans la lignee hematopoietique qui produit les megacaryocytes, precurseurs des plaquettes sanguines. Nous nous sommes attaches a l'etude de l'expression specifique du gene mpl dans la lignee megacaryocytaire. Ce gene code le recepteur a la thrombopoietine, qui intervient dans la proliferation et dans la differenciation des megacaryocytes, et qui est egalement capable de stimuler la proliferation des progeniteurs precoces hematopoietiques. Nous avons montre qu'il est regule par le facteur de transcription gata-1 et des membres de la famille ets. D'autres facteurs pourraient intervenir dans l'expression du gene mpl et notamment des facteurs qui se fixent sur une region intronique qui est une region activatrice quand elle est integree dans la chromatine. Nous nous sommes egalement interesses au facteur de transcription nf-e2 qui agit dans les dernieres etapes de la megacaryopoiese. En effet, des souris depourvues de cette proteine presentent une absence totale de plaquettes. Aucun gene megacaryocytaire cible de cette proteine n'etant connu, nous avons utilise une technique d'immunoprecipitation in vivo, et identifie l'un de ces genes. Il code pour la thromboxane synthetase (txs), qui intervient dans le processus d'agregation des plaquettes. Nous avons montre que le facteur nf-e2 est crucial pour l'expression du gene de la txs dans les megacaryocytes in vivo. La mutation d'un site de fixation pour le facteur nf-e2 dans le promoteur diminue fortement l'activite de ce gene, ce qui confirme que son expression est directement regulee par nf-e2. Notre travail a donc permis d'identifier le premier gene cible du facteur de transcription nf-e2 dans les megacaryocytes.
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37

Zhou, Liwei. "Isolation and characterization of a new gene, SRE, which encodes a Gata-Type Regulatory Protein that controls Iron transport in Neurospora Crassa /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488186329502173.

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38

Philips, Alana Sara Clinical School St George Hospital Faculty of Medicine UNSW. "Molecular insights into the biological role / mechanisms of GATA-4 and FOG-2 in normal cardiac function and in cardiac hypertrophy." Awarded by:University of New South Wales, 2007. http://handle.unsw.edu.au/1959.4/36772.

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The regulation of cardiac-specific genes such as GATA-4 and its co-factor FOG-2 is paramount for normal heart development and function. Indeed, those mechanisms that regulate GATA-4 and FOG-2 function, such as nuclear transport and the post-translational modification of SUMOylation, are of critical importance for cardiogenesis. Therefore the aims of this study were to: i) elucidate the nuclear transport mechanisms of GATA-4; ii) determine the function of SUMOylation on the biological activity of both GATA-4 and FOG-2; and iii) examine how these mechanisms impact on the role of GATA-4 and FOG-2 in cardiac hypertrophy. Firstly, we characterised a non-classical nuclear localisation signal that mediates active import of GATA-4 in both HeLa cells and cardiac myocytes. Fine mapping studies revealed four crucial residues within this region that interacted with importin ?? to mediate GATA-4 import via the non-classical import pathway. In addition, a cardiac myocyte-specific CRM1-dependent nuclear export signal, which consists of three essential leucine residues, was identified. We also investigated the residues of GATA-4 that are responsible for its DNAbinding activity and therefore transcriptional control of cardiac-specific genes. Secondly, we demonstrated that SUMOylation of both GATA-4 and FOG-2 is exclusively carried out by SUMO-2/3. Moreover, SUMOylation is involved in the nuclear localisation of both GATA-4 and FOG-2 in cardiac myocytes as well as the transcriptional regulation of cardiac-specific genes, such as cardiac troponin I. Finally, and perhaps most biologically significant, we showed that nuclear transport as well as SUMOylation of GATA-4 is imperative for the ability of GATA-4 to induce cardiac hypertrophy. Moreover, it was determined that FOG-2 SUMOylation is involved in the ability of FOG-2 to protect against cardiac hypertrophy. In conclusion, the current study provides detailed information on the nuclear transport pathways of GATA-4 as well as the SUMOylation of both GATA-4 and FOG-2 and the role these two mechanisms play in gene transcription and cardiac hypertrophy.
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39

Fayyad, Kazan Mohammad. "Investigation of the molecular mechanisms controlling Nitrogen Catabolite Repression-sensitive gene expression in Saccharomyces cerevisiae." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209287.

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Nitrogen Catabolite Repression (NCR) is the regulatory pathway through which Saccharomyces cerevisiae reduces the expression of genes encoding components involved in the utilization of poor nitrogen sources when rich ones are available. Expression of NCR-sensitive genes is controlled by the negative regulator Ure2 and four DNA-binding GATA-like transcription factors: two activators (Gln3 and Gat1) and two repressors (Dal80 and Gzf3). In the presence of preferred nitrogen sources, Gln3 and Gat1 are sequestered in the cytoplasm in a Ure2-dependent manner, whereas upon growth under non-preferred nitrogen conditions, the GATA activators relocate to the nucleus and mediate the transcription of NCR-sensitive genes. Even though the Target of Rapamycin Complex 1 (TORC1) as well as several phosphatases are involved in regulating Gln3 and Gat1 subcellular localization, a detailed mechanistic understanding of the NCR process is still lacking.

In the first part of this work, we have shown that class C and D VPS (vacuolar protein sorting) components, involved in Golgi-to-vacuole vesicular trafficking, are required for intact Gat1 and Gln3 nuclear localization in response to TORC1-inhibiting rapamycin treatment or upon shifting cells from rich to poor nitrogen conditions. The requirements of Vps proteins for Gln3 function are media-specific: a requirement after rapamycin treatment was observed in minimal but not in rich medium. Moreover, we have seen that a significant fraction of Gat1, like Gln3, is associated with light intracellular membranes. These observations support the view that GATA factor regulation in response to nitrogen signals seems to occur at intracellular compartments.

In a second step, we confirmed an important role for the anabolic glutamate dehydrogenase (Gdh1) within NCR, through the control of Gat1 function. However, since we observed a strong correlation between the anabolic activity of Gdh1 and its NCR regulatory capacity, we do not exclude that an alteration of Gdh1-substrates or any other metabolite could be responsible for the phenotype exhibited by gdh1 mutants. We also showed that there is no simple and direct link between the intracellular levels of glutamine/glutamate (reported in the literature as signals for NCR), TORC1 activity and NCR. In conclusion, the mechanisms regulating the perception of the quality of the nitrogen sources are still not fully understood.

Several screens for multi-copy suppression of mutated phenotypes were conducted during this work and led to the identification of several elements (URE2, BAP2, STP2, GZF3 and KDX1) that could interfere with NCR-sensitive gene expression. Among these, the gene encoding the Kdx1 kinase was identified in two independent screens.

In the last part of this work, we uncovered a role for leucine in NCR signaling. We showed that the addition of leucine in the culture medium could impair Gat1-dependent expression of certain NCR genes, while leucine starvation had no effect at this level. The repressive effect of leucine appeared to involve elements of the SPS signaling pathway which is required for the induction of genes encoding amino acid transporters in response to extracellular amino acids. The mechanism(s) by which leucine regulates Gat1 function is still not fully clear and requires further investigation:La levure Saccharomyces cerevisiae adapte l’expression de ses gènes selon la disponibilité en azote dans son environnement au moyen d’un contrôle majeur appelé répression catabolique azotée (NCR, pour « nitrogen catabolite repression ». L’expression des gènes NCR est contrôlée par un régulateur négatif de type prion (Ure2) et quatre facteurs de transcription de type GATA :deux activateurs, Gat1 et Gln3 et deux répresseurs, Dal80 et Gzf3. Bien que le complexe TORC1 et les phosphatases qu’il régule soient impliquées dans la régulation NCR, le mécanisme précis par lequel la NCR se produit est loin d’être compris.

Dans la première partie de ce travail, nous avons montré que les composants VPS (vacuolar protein sorting) de classe C et D, impliqués dans le trafic vésiculaire entre le Golgi et la vacuole, sont requis pour que Gat1 et Gln3 rejoignent le noyau en réponse à un traitement par la rapamycine, un inhibiteur de TORC1. En accord avec cette observation, nous avons montré que Gat1, comme Gln3, est associé aux membranes intracellulaires légères.

Dans un second temps, nous avons confirmé un rôle important pour la glutamate déshydrogénase anabolique (Gdh1) au sein de la NCR, par l’intermédiaire du contrôle de la fonction de Gat1. Cependant, étant donné qu’il semble exister une forte corrélation entre l’activité anabolique de Gdh1 et sa capacité à réguler la NCR, nous n’excluons pas qu’une altération des substrats de Gdh1 ou de tout autre métabolite pourrait être responsable du phénotype observé du mutant gdh1. Nous avons également montré qu’il n’existait pas de lien simple et direct entre niveaux intracellulaires de glutamine/glutamate, activité de TORC1 et signalisation NCR. En conclusion, les mécanismes conditionnant la perception de la qualité de l’aliment azoté sont encore méconnus à ce jour.

Plusieurs cribles de suppression multicopie ont été menés pendant ce travail et ont conduit à l’identification de plusieurs éléments pouvant éventuellement intervenir dans la voie de signalisation NCR. Parmi ceux-ci, le gène codant pour la kinase KDX1 a été identifié à deux reprises. Nous avons caractérisé en détail le rôle qu’elle joue dans la régulation des gènes NCR.

Dans la dernière partie de ce travail, nous avons montré que l’addition de leucine dans le milieu de culture pouvait affecter l’expression Gat1-dépendante de certains gènes NCR, alors que par ailleurs une carence en leucine est sans effet à ce niveau. Cet effet de répression par la leucine semble nécessiter des éléments de la voie de signalisation SPS, requise pour l’induction, en réponse aux acides aminés extracellulaires, de gènes codant pour des transporteurs d’acides aminés.


Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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40

Hermitte, Stephanie. "Caractérisation de la différenciation de l'endoderme primitif : Coopération entre la voie de signalisation RTK-FGF et le facteur de transcription Gata 6." Thesis, Université Clermont Auvergne‎ (2017-2020), 2017. http://www.theses.fr/2017CLFAS014.

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A E3.5 jours de développement (E3.5), l’embryon murin se compose d’une monocouche de cellules externes correspondant au Trophectoderme (TE) et d’une masse cellulaire interne (MCI), hétérogène, constituée de deux sous-populations de cellules précurseurs : les cellules épiblastiques (Epi) et les cellules d’endoderme primitif (EPr). NANOG, marqueur épiblastique et GATA6, marqueur de l’EPr, sont co-exprimés à E3.5 dans la MCI puis adoptent une expression exclusive au sein de leur lignage respectif. La différenciation du lignage EPr nécessite l’expression de GATA6 et l’activation de la voie Récepteur Tyrosine Kinase (RTK) activée par le FGF (RTK-FGF) pour l’induction de gènes cibles de GATA6 tels que Sox17 et Gata4.Au cours de ma thèse, j’ai, dans un premier temps, étudié la relation GATA6/voie RTK-FGF lors de l’induction de l’expression des gènes de différenciation de l’EPr. J’ai utilisé des cellules souches embryonnaires murines ES sauvages ou mutantes pour Gata6 (ES Gata6-/-), dans lesquelles j’ai surexprimé différentes formes mutantes de Gata6 inactivées sur les différents résidus identifiés comme potentiellement phosphorylables par la voie RTK-FGF. Ainsi, j’ai analysé l’expression protéique des gènes Sox17 et Gata4 ainsi que des expressions ARN de ces cibles et d’autres gènes caractéristiques exprimés dans l’EPr dans les différentes conditions de surexpression des formes de Gata6 en absence ou présence d’inhibiteurs de la voie RTK-FGF. Ainsi, j’ai pu mettre en évidence que la transmission du signal s’effectue au travers de récepteur au FGF et qu’il existe une compensation entre les branches RTK-MEK-ERK et RTK-PI3K ciblant le résidu Sérine 37 de GATA6. Enfin, les résidus S34 et T509 sont nécessaires et les résidus S34, S37 et T509 semblent coopérer, au travers d’un mécanisme pour le moment non détaillé, pour l’induction des gènes cibles exprimés au sein de l’EPr.Dans un second temps, j’ai débuté la caractérisation phénotypique du rôle des facteurs Dickkopf1 (DKK1), un inhibiteur de la voie WNT/β-caténine, et NOGGIN, un inhibiteur de la voie des Bone Morphogenic Protein (BMP) lors de la différentiation de l’EPr en endoderme pariétal (EP) et viscéral (EV). A l’aide de modèles de souris KO pour DKK1 et NOGGIN, croisées en fond C57Bl6 pur, j’ai pu observer que l’expression d’OCT4 était maintenue au sein des embryons homozygotes mutants pour Dkk1 et double homozygotes mutants pour Dkk1 et Noggin. Cependant, le mécanisme potentiel de compensation ou de coopération de ces deux marqueurs n’est pour le moment pas détaillé précisément et mérite l’analyse d’un plus grand nombre d’embryons mutants
At E3.5 days of development (E3.5), mouse embryo consists of a monolayer of external cells corresponding to Trophectoderme (TE) and of an intern cell mass (ICM), heterogeneous, constituted by two subpopulations of precursory cells: epiblastic cells (Epi) and primitive endoderm cells (EPr). NANOG, an Epi marker and GATA6, a PrE marker, are co-expressed at E3,5 in the MCI and then adopt an exclusive expression within their respective lineage. EPr differentiation requires both expression of GATA6 and RTK pathway, activated by FGF ligand, in order to induce late markers Sox17 and Gata4 expression.First, I studied the relation GATA6/RTK during this process to understand the mechanism of induction of these target genes during final EPr differentiation. I used embryonic stem cells ES WT or Gata6 mutants (ES Gata6-/-), in which I transfected various Gata6 mutant constructions on different residues characterized as potentially phosphorylable by the RTK pathway. So, I analyzed protein expression of Sox17 and Gata4 target genes as well as RNA expression of characteristic genes expressed in the EPr in different inhibition conditions of RTK pathway. So, I was able to highlight that the transmission of the signal is made through the FGF receptor (FGFR1) and that there is compensation between RTK-MEK-ERK and RTK-PI3K pathways highlighted by later Gata6 overexpression of certain mutant forms. Finally, residue S34, S37 and T509 seems to cooperate, through a mechanism not detailed for the moment, for the induction of the EPr target genes.Then, I was interested to phenotypically characterize the role of Dickkopf1 (DKK1), an inhibitor of the WNT/β-catenin pathway, and NOGGIN, an inhibitor of the Bone Morphogenic Protein (BMP) pathway during the EPr differentiation in parietal endoderm (EP) and visceral (EV). Using models of mouse KO for Dkk1 and Noggin, met in pure background C57Bl6, I was able to observe that OCT4 expression was maintained within the Dkk1-/-, and Dkk1-/- Noggin-/- embryos. However, the potential compensation or cooperation mechanism of these two markers is not understanding well for the moment and deserves the analysis of a largest mutant embryos number
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41

Velupandian, Uma Maheshwari. "The diagnosis of Patent Foramen Ovale, its importance in migraine, and an insight into its genetic basis." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/the-diagnosis-of-patent-foramen-ovale-its-importance-in-migraine-andan-insight-into-its-genetic-basis(d13d4a0b-b1f3-437a-899a-960015f9b33f).html.

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Background: Patent Foramen Ovale (PFO), a remnant of the foetal circulation, is emerging as a new cause of disease. It has been found to be associated with cryptogenic stroke in young adults, peripheral arterial embolism and neurological decompression sickness in divers. The detection of PFO remains a diagnostic challenge; transoesophageal echocardiogram being currently considered the ‘gold standard’. The development of a non-invasive technique is crucial for the identification of a venous-to-arterial shunt (v-aCS) which may permit paradoxical embolism. Little is known about the genetic basis of PFO and our limited knowledge is based on animal studies and gene mutations detected in patients with other cardiac septal defects. Methods: Study 1: PFO Detection and Evaluation: This study was designed to evaluate transcranial Doppler (TCD), transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) with administration of contrast via arm and femoral veins. We then developed a standardized protocol for PFO detection and quantification using TCD. Study 2: PFO and Migraine: The PFO detection protocol developed from the first study formed the diagnostic technique to detect v-aCS in an adequately powered matched case control study to explore the association between PFO and migraine. Study 3: The Genetic basis of PFO: This study was designed to explore the genetic basis of a PFO using a candidate gene approach. Results: Study 1 - PFO Detection Study: When compared with TOE with femoral vein contrast injection as the ‘gold standard’, TCD with arm vein contrast was 100% sensitive and 97.4% specific for detecting a PFO. We defined a PFO positive (+ve) study on TCD as > 15 microbubbles entering the cerebral circulation, on TCD following arm vein injection and >16 microbubbles with a femoral contrast injection. A ‘major’ PFO+ve v-aCS was defined as >35 microbubbles with arm vein injection or >90 microbubbles with femoral vein injection. We then developed a new diagnostic pathway for PFO detection in clinical practice. Study 2 - PFO Migraine study: A significant difference in prevalence of v-aCS between migraine with aura M+A) and their matched controls was demonstrated with adjusted OR=3.72 (1.48-9.38) p=0.005 for a PFO+ve v-aCS, and a highly significant difference between M+A and controls for a ‘major’ PFO+ve v-aCS with adjusted OR = 6.38 (1.89 – 21.48) p = 0.003. There was significant association with APC resistance and migraine on thrombophilia screen. Study 3 - The PFO Genetics Study: This study detected mutations of GATA4 and NKX2-5 in both PFO+ve cases and PFO-ve controls. Two novel non synonymous mutations of GATA4, c.461T>A and c.994G>A were found only in PFO positive individuals and may be associated with a PFO. All the PFO+ve cases with a GATA4 gene mutation had a major PFO+ve v-aCSConclusion:TCD detects PFO with a sensitivity of 100% and specificity of 92.3% and is the most reliable non-invasive technique for PFO detection. When arm vein injections are used both cough and valsalva provocation is essential. There was a highly significant association between PFO+ve v- aCS and M+A, especially with a ‘major’ PFO+ve v-aCS. GATA 4 mutations though infrequent were found PFO+ve cases and all had major v-aCS.
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Xi, Zong-Fang. "Opposing effects of two zinc finger genes, EVI-1 and GATA-1, on all-trans retinoic acid-induced NB4 cell granulocytic differentiation." Diss., The University of Arizona, 2000. http://hdl.handle.net/10150/284255.

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In hematopoietic stem cells, lineage specific differentiation is determined in part by specific transcription factors which stabilize a particular lineage network and activate differentiation programs. In myeloid and erythroid lineages, distinct transcription factors are expressed in committed progenitors and more differentiated cells. Zinc finger transcription factors, EVI-1 and GATA-1, are expressed in hematopoietic stem cells. Abnormal EVI-1 expression is associated with some human acute myeloid leukemias (AML). It has been shown that enforced EVI-1 expression blocked erythroid specific transcription factor, GATA-1, mediated transcriptional activation and erythroid differentiation. The regulation and the function of the EVI-1 in myeloid differentiation and possible antagonism of erythroid/myeloid lineage transcription factors in lineage commitment and differentiation were studied in NB4, a human acute promyelocytic leukemia (APL) cell line. EVI-1 and GATA-1 were stably expressed in NB4 cells by transfection and effects evaluated on granulocyte differentiation induced by all-trans retinoic acid (ATRA). The results showed that EVI-1 expressing NB4 clones differentiate more rapidly and more completely than control clones. In contrast, GATA-1 expressing NB4 clones showed delayed differentiation. These findings demonstrate that EVI-1 expression promotes and GATA-1 expression delays ATRA-induced NB4 cell granulocytic differentiation, suggesting that EVI-1 plays an important role in myeloid differentiation and EVI-1 and GATA-1 antagonize each other in erythroid/myeloid commitment and differentiation.
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43

BORIES, DOMINIQUE. "Contribution a l'etude de la regulation de l'expression des genes : etude d'un nouveau membre de la famille des facteurs de transcription se liant aux sequences gata, hgata-3." Paris 7, 1994. http://www.theses.fr/1994PA077013.

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Nous avons isole l'adnc et caracterise hgata-3, facteur de transcription lymphocytaire t, homologue aux membres de la famille gata par son domaine de fixation a l'adn en doigt a zinc. Il fixe la sequence consensus a/t gata a/g et transactive le gene de la chaine du recepteur t a l'antigene dont l'enhancer e4 contient deux sites. Le gene hgata-3 se situe sur le chromosome 10(p11-15) et est compose de 6 exons dont le premier est non codant. La region du promoteur, situee dans un ilot cpg, comporte, en transfection transitoire, deux regions inhibitrices, en 5' et en 3' de l'initiation et une region activatrice dans la region du premier intron, sans tissu-specificite. En transfection stable, l'expression du cosmide (3 kb en 5', l'unite de transcription et 6 kb en 3') est tissu-specifique, montrant que les sequences responsables sont situees en 3' de l'initiation. La proteine est etudiee grace a l'aide d'anticorps obtenus contre l'extremite nh2-terminale et de mutants de deletion. Deux regions transactivatrices sont identifiees en nh2-terminal: act i (aa 31 a 59) et act ii (132 a 214). En fusion heterologue, seul act i est transactivateur. D'autres deletions montrent que le doigt cooh-terminal est necessaire et suffisant pour la fixation specifique a l'adn. La deletion minimale (aa 249 a 311) de deux motifs de localisation nucleaire et du doigt nh2-terminal, est necessaire a la perte de la localisation nucleaire exclusive. L'expression de hgata-3, essentiellement dans les lymphocytes t au cours de la vie postnatale, des le stade double negative dans le thymus et juste avant les rearrangements dans le thymus embryonnaire, son activite sur les sequences regulatrices de genes tissu-specifique, en font un candidat au role de regulateur/coordinateur de la differenciation t
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44

Ferreira, Marisa João Horta. "Caracterização clínica e molecular de um caso de síndrome de hipoparatiroidismo, surdez e displasia renal." Master's thesis, 2017. http://hdl.handle.net/10400.6/8074.

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Introdução: A síndrome de hipoparatiroidismo, surdez e displasia renal (HDR - Hypoparathyroidism, Deafness and Renal dysplasia) é uma endocrinopatia autossómica dominante com origem em mutações inativadoras do gene GATA3 (GATA binding protein 3). O gene GATA3, localizado no cromossoma 10p14-15, codifica um fator de transcrição que regula a expressão de genes envolvidos no desenvolvimento embrionário. A síndrome HDR é muito rara, havendo apenas cerca de 100 famílias descritas na literatura mundial. Doentes e métodos: Estudou-se um doente do sexo masculino com hipoparatiroidismo primário diagnosticado aos 51 anos de idade na sequência da investigação de uma crise convulsiva por hipocalcémia. Apresentava ainda uma insuficiência renal crónica de estadio 3b, de duração indeterminada, e uma surdez neurosensorial congénita. Como antecedentes familiares, apresentava o pai com surdez congénita, falecido aos 69 anos de idade com insuficiência renal. Para o estudo genético procedeu-se ao isolamento do ácido desoxirribonucleico (DNA) genómico do propositus, à amplificação dos exões 2 a 6 do gene GATA3 por reação de polimerização em cadeia (PCR) e à análise das respetivas sequências por sequenciação automatizada. Resultados: A sequenciação do gene GATA3 revelou uma inserção de quatro nucleótidos (CAAG), no exão 3, entre as posições 357 e 358 da sequência do respetivo DNA complementar (cDNA) (c.357_358insCAAG). Esta mutação estava presente em heterozigotia e foi confirmada através da análise de heteroduplexes. Discussão e conclusão: A mutação c.357_358insCAAG, identificada no gene GATA3, condiciona uma alteração do tipo frameshift com a introdução de um codão de terminação prematuro e produção de uma proteína truncada. A haploinsuficiência, decorrente da perda funcional de um dos alelos GATA3, tem como consequência provável a alteração da transcrição de genes importantes para o desenvolvimento das paratiróides, rins e ouvido interno. Esta mutação, até ao momento atual, ainda não se encontra descrita e alarga o espectro de mutações implicadas em casos de síndrome HDR.
Introduction: The Hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome is an autosomal dominant endocrinopathy caused by inactivating mutations in the GATA3 gene. The GATA3 gene which is located on chromosome 10p14-15 and encodes a transcription factor that regulates the expression of genes involved in embryonic development. The HDR syndrome is very rare with only about 100 families reported in the literature. Patients and methods: We studied a man with primary hypoparathyroidism diagnosed at 51 years of age, after the investigation of a seizure crisis due to hypocalcaemia. He also presented a stage 3b chronic kidney disease, and a neurosensorial congenital deafness. As family history, his father presented congenital deafness, and died at 69 years of age with chronic kidney disease. For the genetic study, we proceeded to the isolation of genomic deoxyribonucleic acid (DNA) of the patient, the amplification of exons 2 to 6 of the GATA3 gene by polymerase chain reaction (PCR) and analysis of the sequences by automated sequencing. Results: The sequencing of the GATA3 gene showed an insertion of four nucleotides (CAAG) in exon 3, between the positions 357 and 358 of the cDNA sequence (c.357_358insCAAG). This mutation was present in heterozygosity and was confirmed by analysis of heteroduplexes. Discussion and conclusion: The c.357_358insCAAG mutation, identified in the GATA3 gene, determines a frameshift change with the introduction of a premature termination codon and the production of a truncated protein. The haploinsufficiency due to functional loss of one GATA3 allele is likely to change the transcription of genes important for the development of the parathyroids, kidneys and inner ear. This mutation, until now, has not yet been described and extends the spectrum of mutations involved in cases of HDR syndrome.
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45

Cong-KaiLuo and 羅琮凱. "Gata6 gene downregulation enhances rat glioma growth and invasion." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/k6n74j.

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46

Lee, Pei Yun. "Function and Regulation of the Strongylocentrotus purpuratus gatae Gene." Thesis, 2007. https://thesis.library.caltech.edu/1290/4/PYLthesis.pdf.

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The Strongylocentrotus purpuratus gatae is orthologous to vertebrate gata4/5/6 genes. gatae is expressed throughout embryogenesis, beginning in the 15 h blastula in presumptive mesoderm cells, and at mesenchyme blastula, in endoderm and mesoderm cells of the veg2 lineage. During gastrulation, gatae is expressed in the midgut, hindgut and mesoderm, while in the pluteus expression it is limited to the midgut and coelomic pouches. Perturbation of gatae expression resulted in the lowered RNA levels for many endomesoderm transcription factors, including foxA, brachyury, and [beta]1/2-otx, highlighting Gatae’s role as a regulator of transcription factors. gatae occupies an important node in the endomesoderm gene regulatory network, using its cross-regulatory interactions with otx to stabilize the endomesoderm gene expression program. Cis-regulatory analysis of gatae identified two modules responsible for its embryonic expression. Module 10 drives endomesoderm expression in the blastula, while module 24 activates gut expression in the gastrula and pluteus. Deletion of module 10 from a gatae GFP BAC resulted in a complete loss of blastula stage expression, demonstrating its necessity and sufficiency for early activity. Global cis-regulatory analysis of the gatae locus suggests that module usage is exclusionary; only one module can associate with the basal transcriptional apparatus and affect gene transcription at any given time. The endomesoderm gene regulatory network predicts that gatae is downstream of Otx and Notch signaling. Analysis of the sequence of module 10 identified Otx and Suppressor-of-Hairless (Su(H)) binding sites. Injection of Otx-engrailed RNA repressed the expression of module 10:GFP reporter; the effect is abolished when Otx binding sites were mutated. Gel shifts demonstrated that the Otx protein binds to module 10. Module 10 expression was reduced under perturbation of Notch signaling. Mutations of either Otx or Su(H) binding sites resulted in lowered GFP RNA levels with no effect on spatial expression. Mutations of both Otx and Su(H) binding sites led to a further reduction but not elimination of reporter expression, suggesting that another input is involved. This unknown input was determined to be also downstream of Notch signaling and that gatae regulation functions via OR logic.
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47

Kung-wei and 陳官緯. "Chronic lymphocytic leukemia disease-causing genes MLL and DLEU7 gene sequence is associated with GATA transcription factors and possible gene regulation in bioinformatics analysis." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/46443935596986056952.

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碩士
中山醫學大學
口腔生物暨材料科學研究所
99
Genomic aberrations were detected in over 80% of CLL. Chromosomal aberrations occur frequently in CLL, including 13q deletions (∼ 50%), 11q23 deletions (18%). That 13q14 contains two tumor suppressors, miR-15/16 and DLEU7.DLEU7 functions as NF-κB inhibitor in a pathway critical for the pathogenesis of CLL. DLEU7 promoter was methylated in 61% of CLL. MLL gene is a frequent target for recurrent chromosomal translocations found in human acute leukaemias. MLL protein mediated H3/K4 HMT activity. The resulting local MLL H3/K4 HMT activity is thought to promote transcription elongation and maintenance. MLL translocations are associated with distinct patterns of DNA methylation. CLL cells exhibit telomere dysfunction. Telomere damage response,MLL is directly responsible for the upregulated transcription of TERRA. GATA-1, GATA-2,and GATA-3 are termed the hematopoietic GATA factors, based on their important activities to control distinct and overlapping aspects of hematopoiesis. The comprehensive knowledge of transcription factor binding sites (TFBS) is important for a mechanistic understanding of transcriptional regulation as well as for inferring gene regulatory networks. The research use some Bioinfomatic software to predict TFBS、promoter in MLL gene ,and predict TFBS、promoter and splicing site in DLEU7 gene. The research show that GATA transcription factors are likely to direct participation in the regulation of MLL and DLEU7 gene expression. And discuss this potentially interacting TFs.
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48

Lamoureux, Lise Marie. "Regulation of calreticulin gene by bHLH and GATA-1 proteins." 2004. http://hdl.handle.net/1993/16296.

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49

Eisbacher, Michael. "The regulation of megakaryocyte-specific genes by Fli-1 and GATA-1 /." 2003. http://www.library.unsw.edu.au/~thesis/adt-NUN/public/adt-NUN20040206.105222/index.html.

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50

"Funções do gene GATA1 : contribuições do estudo de mutações em doenças hematologicas." Tese, Biblioteca Digital da Unicamp, 2006. http://libdigi.unicamp.br/document/?code=vtls000405552.

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