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1

Cleavinger, Peter Jay. "Role of the long terminal repeat in transcriptional regulation of rous sarcoma virus gene expression." free to MU campus, to others for purchase, 1996. http://wwwlib.umi.com/cr/mo/fullcit?p9841207.

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2

Chen, Di. "Regulatory pathways controlling larval development in caenorhabditis elegans." Free to MU Campus, others may purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p3144405.

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3

Blackwell, Gemma. "Regulation of flagellin glycosylation genes in Campylobacter jejuni : influence of NssR, the nitrosative stress response regulator." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/639/.

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Campylobacter jejuni is one of the leading causes of food borne illness worldwide; the main cause of infection is the consumption of undercooked, contaminated poultry. Motility, mediated by single polar flagella, is necessary for Campylobacter virulence. The flagellin proteins are extensively glycosylated in C. jejuni with pseudaminic acid and related derivatives; glycosylation is required for flagella filament formation. The flagellin glycosylation locus in C. jejuni NCTC11168 comprises 50 genes, 50% are potentially involved in glycan biosynthesis and others are hypothetical; the regulatory mechanism(s) of flagellin glycosylation remain unclear. The response to nitric oxide stress in C. jejuni is regulated by NssR, which also regulates a small number of genes in the flagellin glycosylation locus; an nssR mutant has defective motility. This work aims to elucidate the mechanisms by which NssR regulates these genes and investigate the consequences of nssR mutation. Transcriptional organisation of the affected genes was deduced and chromatin immunoprecipitation (ChIP) used to map NssR binding to six potential locations in the region. Methods to measure bacterial motility were assessed and used to document the defective motility of the nssR mutant, which was found to be due to truncated, sometimes asymmetric, flagella. Finally, mass spectrometry was used to examine flagellin glycosylation in all strains.
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Messenger, Sarah Louise. "Aerobic activity of FNR : the anaerobic transcription regulator of Escherichia coli." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391167.

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5

Smeds, Johanna. "Role of the CDKN2A and related cell cycle regulatory genes in melanoma and other human cancers /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-105-5/.

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6

Cordeiro, André Miguel Henriques. "The rice Phytochrome-Interacting Factor 14 – a regulator of cold, jasmonic acid and light related genes." Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica António Xavier, 2017. http://hdl.handle.net/10362/77055.

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"Rice (Oryza sativa L.) is the staple food for more than half of the world population, and it is very sensitive to adverse environmental conditions. It is also very important for Portugal, which is the biggest rice consumer in Europe with a consumption of 14.8 kg/capita/year. Nowadays, due to climate changes and competition with other crops, the arable land for rice is decreasing. To overcome this and feed the growing world population, keeping the prices affordable, it is estimated that rice yield needs to grow 1.0–1.2% annually beyond 2020. Therefore, it is urgent to develop rice with higher grain yield and more resistant to adverse environmental conditions.(...)"
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7

Kanth, Anna. "Studies on global regulators involved in virulence gene expression in Staphylococcus aureus /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-494-1/.

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8

Christensen, Kimberly Laura. "The developmental regulator SIX1 plays multiple roles in breast cancer initiation and progression /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.

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Thesis (Ph.D. in Biophysics & Genetics, Program in Molecular Biology) -- University of Colorado Denver, 2007.
Typescript. Includes bibliographical references (leaves 115-132). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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9

Goymer, Patrick. "The role of the WspR response regulator in the adaptive evolution of experimental populations of Pseudomonas fluorescens SBW25." Thesis, University of Oxford, 2002. http://ora.ox.ac.uk/objects/uuid:52629a69-2863-4d90-8193-641ed91c286b.

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The role of ecological opportunity in adaptive radiation has been demonstrated by the diversification of the bacterium Pseudomonas fluorescens SBW25 in a spatially structured microcosm. This provides an ideal system for studying the genetics of adaptation and asking questions about the genes that matter in evolution. Previous studies have identified the genes that are necessary for the evolved, biofilm-forming, niche-specialist genotype, the wrinkly spreader (WS). These genes are organised in two operons: the wss operon that encodes the genes for cellulose biosynthesis, and the wsp operon that encodes a chemosensory pathway. The terminal gene in the wsp operon, wspR, encodes a novel response regulator thought to regulate the activity of the wss operon. This gene forms the basis of this study, which assesses the role of regulatory genes in adaptive evolution. The structure-function relationship of WspR is established through the phenotypic analysis of overexpressed wspR random point mutants. On this basis a model of WspR activity is proposed which is tested by molecular genetic analysis. The role of phosphorylation is demonstrated by site-directed mutagenesis, and domain liberation is used to study the interaction of WspR with the other components of the signalling pathway. As the overexpression of certain wspR mutant alleles mimics the evolutionary transition from ancestor to niche-specialist, the fitness effects of such overexpression are measured. It is found that some, but not all, wspR alleles do indeed cause adaptation. It is also found that a phenotypically-plastic genotype, with enhanced fitness, can be created by artificial manipulation, but does not occur naturally; this demonstrates the existence of a constraint on evolution. Sequence analysis of independently-isolated WS genotypes shows no evidence of wspR sequence variation, despite its capacity to enhance fitness. A further proteomic and phenotypic characterisation shows variation between ancestral and WS genotypes, and also between different WS genotypes. This demonstrates that there are different mutational routes to the same adaptation.
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Chen, Hsiuyi V. "Systematic Dissection of Roles for Chromatin Regulators in Dynamics of Transcriptional Response to Stress in Yeast: A Dissertation." eScholarship@UMMS, 2015. http://escholarship.umassmed.edu/gsbs_diss/808.

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The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me to identify specific interactions between histone modifications and chromatin modifiers. Furthermore, by combining these functional results with genome-wide mapping of several histone modifications in the same time course, I was able to investigate the correspondence between histone modification occurrence and function. One such observation was the role of Set1-dependent H3K4 methylation in the repression of ribosomal protein genes (RPGs) during multiple stresses. I found that proper repression of RPGs in stress required the presence, but not the specific sequence, of an intron, an element which is almost unique to this gene class in Saccharomyces cerevisiae. This repression may be related to Set1’s role in antisense RNA-mediated gene silencing. Finally, I found a potential role for Set1 in producing or maintaining uncapped mRNAs in cells through a mechanism that does not involved nuclear exoribonucleases. Thus, deletion of Set1 in xrn1Δ suppresses the accumulation of uncapped transcripts observed in xrn1Δ. These findings reveal that Set1, along with other chromatin regulators, plays important roles in dynamic gene expression through diverse mechanisms and thus provides a coherent means of responding to environmental cues.
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Pasternak, Michał. "RNAi screen for meiotic genes in mammals reveals BTG4 as a novel regulator of meiosis." Thesis, University of Cambridge, 2016. https://www.repository.cam.ac.uk/handle/1810/283984.

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12

Eozenou, Caroline. "FOXL2 : A regulator of endometrial physiology ? First insights from ruminants." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T100/document.

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L’implantation est caractérisée par les premiers contacts cellulaires permanents entre l’endomètre, tapissant l’utérus, et le conceptus (disque embryonnaire et tissus extra-embryonnaires). Cette étape se trouve être l’un des plus importants points de contrôle de la gestation nécessitant un dialogue finement régulé entre ces deux entités. Concernant les ruminants, un déclin de la fertilité a été observé notamment chez les vaches laitières hautes productrices. La moitié des gestations s’arrête pendant la période pré-implantatoire due à des mortalités embryonnaires précoces ainsi qu’à des défauts utérins. Depuis 10 ans, des analyses exploratoires ont été mises en place dans le but d’étudier les profils d’expression de gènes endométriaux sous l’influence du cycle oestral, de la gestation précoce ou encore des stéroïdes ovariens comme la progestérone et les oestrogènes. Ces études sont essentielles pour l’identification des gènes endométriaux clés pour la survie et la croissance du conceptus avant l’implantation. Notre laboratoire a réalisé une analyse transcriptomique à partir d’échantillons endométriaux collectés sur des vaches cycliques et gestantes au 20 ème jour post-oestrus correspondant respectivement à la phase folliculaire et au premier jour d’implantation. Plusieurs familles de facteurs de transcription apparaissent différentiellement exprimées dans cette étude, notamment FOXL2, un membre de la famille des Forkhead Box transcription factor considéré comme le gène clé de la différenciation ovarienne. Ce travail de thèse s’est intéressé à l’implication de FOXL2 dans la physiologie endométriale. FOXL2 est exprimé et régulé pendant le cycle oestral et la gestation précoce dans l’endomètre de ruminants. De plus, la progestérone a été identifiée comme le régulateur majeur de l’expression endométriale de FOXL2 chez la vache et la brebis alors que l’effet des estrogènes n’a pas été démontré. A partir d’une approche gènes candidats, la surexpression de FOXL2 induit la régulation différentielle de onze gènes potentiellement cibles de FOXL2 dans des cultures primaires endométriales de cellules stromales et épithéliales glandulaires. En particulier, PTGS2 qui est un gène impliqué dans la réceptivité utérine apparait inhibé par FOXL2 alors que SCARA5 et RSAD2, tout deux impliqués dans la réponse immunitaire sont stimulés. Enfin, DLX5 apparait différentiellement régulé entre les cellules stromales et épithéliales glandulaires sous l’impact d’une surexpression de FOXL2. Pour conclure, l’expression endométriale de FOXL2 est fortement liée au processus de réceptivité utérine qui se déroule avant l’implantation et peut moduler l’expression de gènes endométriaux essentiels. De nouvelles analyses sont nécessaires pour déterminer si FOXL2 est le gardien de la physiologie reproductive femelle
Implantation is characterized by the first permanent cellular interactions between the endometrium, lining the uterus, and the conceptus (embryonic disk and extra-embryonic tissues) and appears to be one of the most important checkpoints of successful pregnancy. Regarding ruminant species, and more specifically dairy cows, half of pregnancies abort during the pre-implantation period due to early embryonic death and uterine defects. In the last decade, exploratory approaches have been developed to study endometrial genes expression under the influence of oestrous cycle, early pregnancy, and ovarian steroid hormones in order to identify systematically crucial endometrial genes for conceptus growth and survival leading to a successful implantation in ruminant specifically. A microarray analyse made at the laboratory based on endometrial samples collected from cyclic and pregnant cows at 20 days post-oestrous, corresponding respectively to the follicular phase and the implantation initiation. Several members of the transcription factor families appeared to be differentially expressed in this study including FOXL2, a member of the Forkhead box L sub-class originally considered as a key gene for ovarian differentiation. My PhD thesis focused on the implication of FOXL2 gene in endometrial physiology. FOXL2 gene had been demonstrated to be expressed and regulated during the oestrous cycle and early pregnancy in ruminant endometrium. Moreover, progesterone was identified as a master regulator of FOXL2 endometrial expression in both cattle and sheep whereas estrogens have no impact. Based on candidate genes approach, over-expression of FOXL2 gene induces a regulation of eleven putative FOXL2 target genes in primary endometrial stromal and glandular epithelial cells. In particular, PTGS2 which is a positive regulator gene for uterine receptivity was shown to be inhibited whereas SCARA5 and RSAD2 expressions that were involved in immune response were shown to be stimulated as well as DLX5 expression was differentially regulated between stromal and glandular epithelial cells. Collectively, FOXL2 endometrial expression is strongly linked to the uterine receptivity process prior to the implantation and modulates the expression of essential endometrial genes. Further investigations will be required to investigate whether FOXL2 is the gatekeeper of female reproduction in the vertebrate species
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13

Furgeri, Daniela Tenório 1983. "Estudo de polimorfismos nos genes TCF7L2 e ADRA2A associados à gravidade clínica da fibrose cística = Study of polymorphisms in ADRA2A and TCF7L2 genes associated with clinical gravity of cystic fibrosis." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308578.

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Orientador: Carmen Silvia Bertuzzo
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-23T02:22:32Z (GMT). No. of bitstreams: 1 Furgeri_DanielaTenorio_D.pdf: 7382335 bytes, checksum: edfcfca14ac645a69fd4e8e2d2777246 (MD5) Previous issue date: 2013
Resumo: A fibrose cística (FC) é uma doença autossômica recessiva com características de doença complexa. Complicações clínicas parece ser fator decisivo para o prognóstico dos pacientes. Os polimorfismos nos genes ADRA2A e TCF7L2 são importantes para elucidar parte da variabilidade encontrada nas características clínicas de doenças inflamatórias, incluindo a FC, que tem a Diabetes Mellitus como uma importante co-morbidade. Os objetivos deste estudo foram determinar a frequência do polimorfismo rs12255372 no gene TCF7L2 e sua associação com Diabetes Mellitus em pacientes com fibrose cística, e investigar a associação de 27 variáveis clínicas da FC com os polimorfismos rs553668 e rs10885122 do gene ADRA2A. Em nosso estudo, 145 pacientes foram avaliados em relação ao genótipo do polimorfismo rs12255372 no gene TCF7L2 e 176 pacientes foram avaliados em relação à associação dos polimorfismos rs553668 e rs10885122 no gene ADRA2A com 27 variáveis clínicas da FC. Todos os pacientes em atendimento no Ambulatório de Pediatria da Faculdade de Ciências Médicas da UNICAMP foram confirmados como tendo fibrose cística por dois testes de suor alterados (valor de sódio e de cloro superior a 60 mmol / L) e por análise de diferencial do epitélio da membrana do intestino através da dosagem de CFTR pela câmara Ussing. A identificação das mutações do gene CFTR foi realizada no laboratório de Genética Molecular da FCM/Unicamp. O rastreio do polimorfismo rs12255372 foi feito através da técnica de PCR associada à digestão enzimática específica. O rastreio dos polimorfismos rs553668 e rs10885122 no gene ADRA2A foi feito por PCR ARMS. Uma comparação genotípica foi realizada com as 27 variáveis clínicas, da FC considerando as mutações do gene CFTR. Encontramos associações clínicas, sem considerar as mutações no gene CFTR, com as variáveis categóricas: raça [para o polimorfismo rs553668 (p = 0,002), grupo haplotípico (p = 0,014)], íleo Meconial [para o polimorfismo rs553668 (p = 0,030) Quando consideradas as duas mutações no gene CFTR, encontramos associações com as variáveis íleo meconial (p = 0,0012) e IMC [para o polimorfismo rs553668 (p = 0,014)]. A associação com dados numéricos, sem considerar as mutações no gene CFTR, foi positiva para a idade ao diagnóstico [para o polimorfismo rs553668 (p = 0,022)]. Considerando as duas mutações no gene CFTR, a associação com dados numéricos foi positiva para o Escore de Bhalla [para o polimorfismo rs553668 (p = 0,014)], Escore de Shwachman-Kulczycki [para o polimorfismo rs553668 (p = 0,008) e haplótipos (p = 0,050)]. Os polimorfismos rs553668 e rs10885122 no gene ADRA2A parecem ser moduladores da gravidade da FC em nossa amostra. Em nossa amostra, não houve associação entre o polimorfismo rs12255372 no gene TCF7L2 e a Diabetes Mellitus
Abstract: Cystic fibrosis (CF) is an autosomal recessive disease with characteristics of complex disease. Clinical complications appear to be a decisive factor in the prognosis of patients. The ADRA2A and TCF7L2 gene polymorphisms are important to elucidate part of the variability encountered in clinical characteristics in inflammatory diseases, including CF, which has diabetes-associated as an important comorbidity. The aims of this study ware to determine the frequency of polymorphism rs12255372 in the TCF7L2 gene and its association with Diabetes Mellitus in Cystic Fibrosis patients and to investigate the association of 27 CF clinical variables with ADRA2A polymorphisms. In our study, 145 patients were evaluated in relation to the genotype of the rs12255372 polymorphism in the TCF7L2 gene. 176 patients were evaluated in relation to associate rs553668 and rs10885122 polymorphisms in the ADRA2A gene with 27 CF clinical variables. All patients in attendance at the Pediatric Clinic at the Faculty of Medical Sciences, UNICAMP, were confirmed as having cystic fibrosis by two altered sweat tests (sodium and chlorine value greater than 60 mmol/L) and by analysis of differential membrane epithelium of the intestine by the dosage of active CFTR through the Ussing chamber. The identification of CFTR gene mutations was performed in the laboratory of Molecular Genetics, FCM/Unicamp. The rs12255372 polymorphism was screening by PCR method associated with specific enzymatic digestion. The rs553668 and rs10885122 polymorphisms in ADRA2A gene were screening by ARMS-PCR. A genotypic comparison was performed with 27 CF clinical variables, considering CFTR mutations. We found clinical associations, without considering the mutations in the CFTR gene, with categorical variables: race [for polymorphism rs553668 (p = 0.002), haplotype group (p = 0.014)], meconium ileus [for polymorphism rs553668 (p = 0.030). Considering the two mutations in the CFTR gene, we find associations with categorical variables meconium ileus (p = 0.0012) and BMI [for polymorphism rs553668 (p = 0.014)]. The association with numerical data, without considering the mutations in the CFTR gene, was positive for age at diagnosis [for polymorphism rs553668 (p = 0.022)]. Considering the two mutations in the CFTR gene, the association with numerical data was positive for Bhalla score [for polymorphism rs553668 (p = 0.014)], Shwachman-Kulczycki score [for polymorphism rs553668 (p = 0.008) and haplotypes (p = 0.050)]. Polymorphisms rs553668 and rs10885122 in ADRA2A gene appear to be modulators of CF severity in our sample. In our sample, there was no association between the polymorphism rs12255372 in the TCF7L2 gene and Diabetes Mellitus
Doutorado
Clinica Medica
Doutora em Clínica Médica
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14

Kimura, Masahiro. "Homeobox A4 Suppresses Vascular Remodeling as a Novel Regulator of YAP/TEAD Transcriptional Activity." Kyoto University, 2020. http://hdl.handle.net/2433/253486.

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15

Pilonieta, Maria Carolina. "Transcriptional Regulation of Virulence Genes in Enterotoxigenic Escherichia coli and Shigella flexneri by Members of the AraC/XylS Family." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/111.

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Pathogenesis of enterotoxigenic Escherichia coli (ETEC) and Shigella flexneri relies predominantly on members of the AraC/XylS family of transcriptional regulators, Rns (or its homolog, CfaD) and MxiE, respectively. Rns/CfaD regulate the expression of pili, which allow the bacteria to attach to the intestinal epithelium. Better understanding of the role Rns plays in virulence was attained by expanding our knowledge of the Rns regulon, revealing that it functions as an activator of cexE, a previously uncharacterized gene. By in vitro DNase I footprinting two Rns-binding sites were identified upstream of cexEp, both of which are required for full activation of cexE. The amino terminus of CexE also contains a secretory signal peptide that is removed during translocation to the periplasm. Though the function of CexE remains unknown, these studies suggest that CexE is a novel ETEC virulence factor since it is regulated by Rns/CfaD. In Shigella flexneri, the expression of a subset of virulence genes (including, ipaH9.8 and ospE2) is dependent upon the activator MxiE and a cytoplasmic chaperone IpgC. To define the molecular mechanism of transcriptional activation by this chaperone-activator pair, an in vitro pull down assay was performed revealing that MxiE specifically interacts with IpgC in a complex. Additionally, IpgC recognizes three polypeptide regions in MxiE: within MxiE(1-46), MxiE(46-110) and MxiE(196-216). Furthermore, it seems that MxiE and IpgC regulate transcription of ipaH9.8 and ospE2 promoters differently. In the bacterium, the formation of the MxiE-IpgC complex is initially prevented because IpgC is sequestered in individual complexes with effector proteins, IpaB and IpaC. Upon contact with an eukaryotic host cell the effector proteins are secreted, thereby freeing IpgC to form a complex with MxiE and activate the expression of virulence genes. This new characterization of the role of Rns and MxiE in virulence gene regulation in ETEC and S. flexneri, respectively will give new insights into the pathogenesis of the regulators.
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Saenz, Charlotte Cesty Borda de. "Estudos de genes envolvidos na via biossintética do antibiótico antitumoral Cosmomicina." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-17042008-092436/.

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Cosmomicina é um antibiótico antitumoral produzido pela bactéria Streptomyces olindensis DAUFPE 5622. Estudos de expressão gênica demonstraram que genes cuja expressão esta relacionada a condições de estresse (dnaJ e 18hsp), assim como genes associados a via biossintética de cosmomicina, são expressos sob condições de produção do antibiótico. Genes que ainda tinham a função desconhecida foram selecionados (cosS e cosY) e foram realizados análises bioinformáticas destes atribuindo-lhes a função de regulador transcricional e ornitina ciclodesaminase, respectivamente. Um cassete para inativação desses genes foi construído visando a futura obtenção de mutantes nulos. Genes de glicosiltransferase (cosK e cosG) também apresentaram diferenças na expressão na presença do antibiótico. Neste trabalho, foi revelada a presença de uma hipotética glicosiltransferase que tem homologia com a B-daunosamine daunomy, glicosiltransferase envolvida na transferência de açúcares na biossíntese do antibiótico daunomicina.
Cosmomycin is an antitumoral antibiotic produced by the soil bacteria Streptomyces olindensis DAUFPE 5622. Gene expression studies established that stress condition genes like dnaJ and 18hsp, and cosmomycin biosynthetic pathways genes are expressed under antibiotic production. Also the genes cosS and cosY (unknowns function), were selected and analyzed by bioinformatics techniques attributing a transcriptional regulator and ornithine cyclodeaminase functions, respectively. A cassette was constructed in order to inactivate these two selected genes and generating void mutants. Another gene cosK, with glycosiltransferase function, also presented differences in its expression when the antibiotic is produced. We described in this work the presence of a hypothetical glycosiltransferase related with B-daunosamine daunomy, which transfers sugar molecules in the biosynthesis of daunomycin antibiotic.
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Engström, Pär. "Gene complexes and regulatory domains in metazoan genomes /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-361-0/.

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Emilsson, Lina. "Detection of Differentially Expressed Genes in Alzheimer's Disease : Regulator of G-protein Signalling 4: A Novel Mediator of APP Processing." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5910.

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Shen, Jian [Verfasser]. "Characterization of drought stress regulator CBF/DREB genes in Hordeum vulgare : Expression analysis in ten different barley cultivars / Jian Shen." Bonn : Universitäts- und Landesbibliothek Bonn, 2013. http://d-nb.info/104497107X/34.

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McBride, Jane. "Purification of Global Regulator, Spx, and RNA Polymerase from Staphylococcus aureus for Use in In Vitro Transcription of Redox Genes." ScholarWorks@UNO, 2006. http://scholarworks.uno.edu/td/495.

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Spx is a global regulator discovered in Bacillus subtilis to suppress basal growth and development processes and activate transcription of genes involved in thiol homeostasis when a cell encounters oxidative stress. Its activity relies on reversible thiol-disulfide bond formation and binding RNA polymerase rather than DNA. The discovery that Staphylococcus aureus global virulence regulator, SarA, is more active upon cysteine reduction suggests that redox response could mediate virulence in this important human pathogen. We describe the cloning of spx from S. aureus strain RN6390, overexpression in Escherichia coli, and purification of native protein. Antibodies against Spx were raised for western analysis. Spx from S. aureus was highly active in a B. subtilis in vitro transcription system, stimulating expression of trxB, the gene encoding thioredoxin reductase, without reducing agents. RNA polymerase was partially purified from S. aureus, and the enzyme was active, catalyzing transcription of rpsD, but not trxB.
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Toukoki, Chadia. "MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus." Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/biology_diss/66.

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Group A Streptococcus (GAS) is a common pathogen of the human skin and mucosal surfaces and is capable of producing a variety of diseases. This dissertation investigates the function of a metalloregulator named MtsR in GAS physiology and disease process. An mtsR mutant was constructed and analyzed. Consistent with MtsR role in iron uptake regulation, the mtsR mutant accumulates more iron (80 ± 22.5%) than the wild type strain. Inactivation of mtsR results in constitutive transcription of the sia (Streptococcal Iron Acquisition) operon, which is negatively regulated by iron in the parent strain. We identified the promoter that controls the expression of the sia operon (Pshr) and used it as a model to study MtsR interaction with DNA. Electrophoretic mobility gel shift assays (EMSAs) demonstrated that MtsR binds to the shr upstream region specifically and in an iron and manganese dependent manner. DNase I footprint analysis revealed that MtsR protects a 69 bp segment in Pshr that includes 2 inverted repeats, overlapping the core promoter elements. A global transcriptional analysis determined that MtsR modulates the expression of 64 genes, of which 44 were upregulated and 20 were downregulated in the mtsR mutant. MtsR controls genes with diverse functions including immune evasion, colonization, dissemination, metal homeostasis, nucleic acid and amino acid metabolism, and protein stability. MtsR functions as a dual regulator as it binds to the promoters of the repressed genes ska, aroE, and nrdF.2, as well as the upstream region of the positively regulated genes mga, emm49, and pyrF. A 16 bp MtsR-binding consensus region was identified in all of the promoters that are directly regulated by MtsR. In conclusion, we have demonstrated that MtsR is a global regulator in GAS that controls the expression of vital virulence factors and genes involved in metal transport, virulence and metabolic pathways.
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Banerjee, Chaitali. "The Osteocalcin Gene: Transcriptional Elements and Factors Regulating TGF-β1 Responsiveness and Tissue-Specific Expression in Bone Cells: A Dissertation." eScholarship@UMMS, 1998. http://escholarship.umassmed.edu/gsbs_diss/145.

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Osteocalcin (OC) is a bone specific protein expressed during differentiation and mineralization of the bone extracellular matrix. The Osteocalcin gene is transcriptionally regulated by several basal, hormone- and cytokine-responsive elements. To address the potential role of TGF-β1 regulation and tissue-specific expression of the OC gene, we defined regulatory elements and factors mediating the transcriptional activity of the rat OC (rOC) promoter. TGF-β1 modulates the differentiation of cells of the osteogenic lineage and downregulates the osteoblast-specific expression of OC. By promoter deletion and mutational analyses, a TGF-β1 responsive element at nt -146 to -139 and a contiguous tissue-specific enhancer element at nt -136 to -130 on the rOC promoter were identified. These studies show that Fra-2, a member of the AP-1 family of proteins, binds to the TGF-β1 responsive element and activates basal OC expression. TGF-β1 induced phosphorylation of Fra-2 inhibits this activation, resulting in repression of OC gene transcription. The tissue-specific enhancer element contiguous to the TGF-β1 responsive element contains an AML (Cbfa) binding sequence. This element, designated OC Box II, contributes to 75% of the basal OC promoter activity and forms an osteoblast-specific protein-DNA complex in in-vitro assays. The activation potential of this binding sequence was established by overexpressing AML (Cbfa) transcription activator proteins in osteoblastic as well as in non-osseous cell lines. Interestingly, overexpression not only enhances rOC promoter activity in osteoblasts but also mediates promoter activity in a non-osseous human fibroblastic cell-line. Subsequently, we identified AML-3 (Cbfa1) as the major AML family member present in the osteoblast specific complex and demonstrate that AML-3 (Cbfa1) is expressed predominantly as a 5.4 kb transcript in rat bone tissues. Finally, to establish the functional involvement of AML (Cbfa) transcription factors in osteoblast differentiation, we utilized antisense strategies to demonstrate that blocking expression of all AML (Cbfa) related genes in primary osteoblast cultures significantly decreased several parameters which are linked to differentiation of normal diploid osteoblasts. These results indicate that AML-3 (Cbfa1) is a key transcription factor in bone cells and that the activity of the AML (Cbfa) family of proteins is required for completion of osteoblast differentiation.
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Argai, Aisha Ayad [Verfasser], Thomas [Akademischer Betreuer] Hollemann, Harald [Akademischer Betreuer] Loppnow, and Alexandra [Akademischer Betreuer] Schambony. "Identification of new target genes of the transcriptional regulator Ets-related protein 71 / Aisha Ayad Argai. Betreuer: Thomas Hollemann ; Harald Loppnow ; Alexandra Schambony." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2015. http://d-nb.info/1065670141/34.

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24

DeShazer, David. "Genetics of virulence in Bordetella pertussis. I. Characterization of genes for superoxide dismutase and catalase. II. Identification of a new putative transcriptional regulator." Diss., The University of Arizona, 1994. http://hdl.handle.net/10150/186803.

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The Bordetella pertussis gene encoding superoxide dismutase (SOD), termed sodB, was cloned. The nucleotide sequence of sodB predicted a 21-kDa protein with homology to iron-containing SODs. Examination of SOD activity gels suggests that B. pertussis extracts contain a single SOD that utilizes Fe³⁺ as its prosthetic group. A SOD-deficient mutant, DD25, was obtained by insertional inactivation of sodB in B. pertussis. DD25 was more sensitive to killing by the superoxide-generating compound paraquat than the parental strain BP339. Both strains survived equally in human polymorphonuclear leukocytes (PMN). Crude extracts of B. pertussis contain a single catalase. B. pertussis katA was cloned and the nucleotide sequence predicted a 55-kDa protein that shared homology with heme-containing catalases. Analysis of the nucleotide sequence upstream of katA revealed the presence of a copy of IS481, a B. pertussis-specific insertion sequence. The start site of transcription of katA was mapped to a T residue in IS481 by primer extension analysis. A catalase-deficient strain of B. pertussis, DD900, was constructed and was more sensitive to H₂O₂ killing than the parental strain BP339. However, there was no difference in the ability of either strain to survive in PMN. The genes encoding pertussis toxin (ptx) and adenylate cyclase toxin (cya) are positively regulated in B. pertussis by the bvgAS locus. However, ptx::lacZ and cya::lacZ transcriptional fusions in E. coli cannot be activated by bvgAS in trans. This suggests that an additional factor(s) is required for transcription of these genes. A gene encoding a Bvg accessory factor (BAF) was identified by it's ability to activate ptx::lacZ in the presence of bvgAS. The expression of ptx::lacZ was decreased by the addition of 40 mM MgSO₄, a compound that also modulates ptx expression in B. pertussis. An additional copy of baf was integrated into the chromosome of BC75, a B. pertussis mutant that expresses low levels of ptx and cya. The defect in BC75 was partially complemented in the cointegrate strain. The gene encoding BAF was localized, sequenced, and found to produce a 28-kDa protein. BAF appears to be a new kind (class) of transcriptional regulator.
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Sammons, Wendy L. "Generation and characterization of an attenuated mutant in a response-regulator gene of Francisella tularensis live vaccine strain (LVS)." [Tampa, Fla.] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0002268.

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Sohlberg, Joel. "Regulation of plant development by the SHI-family of transcriptional regulators /." Uppsala : Dept. of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/200608.pdf.

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27

Sartor, Ivaine Tais Sauthier. "Biologia computacional na identificação dos reguladores mestres da transcrição em câncer pancreático." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/96813.

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O adenocarcinoma de ducto pancreático é reconhecido mundialmente como uma doença extremamente agressiva a qual apresenta um prognóstico desfavorável para pacientes sem cirurgia de ressecção. Portanto, é fundamental ampliar o conhecimento sobre os mecanismos biológicos envolvidos no câncer pancreático a fim de permitir a identificação de marcadores moleculares e alvos terapêuticos com o intuito de melhorar o diagnóstico precoce e tratamento. Os fatores de transcrição, reconhecidos por serem os efetores finais de vias de sinalização, regulam diversas funções celulares e, alterações na expressão transcricional destes podem contribuir para a transformação celular bem como para a progressão tumoral. Assim, o objetivo do presente estudo foi identificar os reguladores mestres da transcrição, possivelmente envolvidos no câncer pancreático. Para tanto, utilizamos dados de microarranjos para associar os reguladores mestres com o fenótipo tumoral. As análises foram realizadas no ambiente estatístico R utilizando os pacotes RTN, Limma e Survival. O gene TULP3 foi identificado como um regulador mestre da transcrição em amostras de câncer pancreático. O valor prognóstico de TULP3 foi verificado através de análises de sobrevivência em três coortes independentes. Estas análises revelaram que pacientes com adenocarcinoma pancreático, exibindo altos níveis de expressão do gene TULP3, apresentam uma sobrevida global desfavorável. Os altos níveis transcricionais de TULP3 podem desempenhar um papel fundamental na progressão do adenocarcinoma pancreático e conduzir a um resultado clínico desfavorável. Contudo, este estudo destaca a potencial aplicação de TULP3 como um biomarcador de prognóstico clínico para pacientes com adenocarcinoma pancreático.
Pancreatic ductal adenocarcinoma is world-wide recognized as an aggressive disease with poor prognosis in patients who did not undergo resection. Efforts to better comprehend the biological mechanisms of pancreatic cancer are needed to enable the identification of novel molecular markers and therapeutic targets for improving early diagnosis and treatment. Transcription factors are the final effectors of signaling pathways and regulate a number of cellular functions. Changes in expression of transcription factors may contribute to cellular transformation and tumor progression. Thus, the aim of the present study was to identify transcriptional master regulators potentially involved in pancreatic cancer disease. To achieve this goal, we utilized microarray data to associate master regulators with tumor phenotype. Analyses were performed with RTN, Limma, and Survival packages at R environment. We identified TULP3 as a master regulator of transcription in pancreatic cancer samples. TULP3 prognostic value was accessed in three independent cohort analyses. Our data demonstrate that patients with pancreatic cancer, exhibiting high TULP3 transcriptional levels, show a poor overall survival. High levels of TULP3 expression may play an essential role in pancreatic cancer progression and lead to poor clinical outcome. Our results highlight the potential use of TULP3 as a clinical prognostic biomarker for pancreatic adenocarcinoma.
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Torres, Maria Alejandra Ferreira. "Análise genômica de Streptomyces olindensis DAUFPE 5622 e de suas vias crípticas para a obtenção de novos metabólicos secundários de interesse biotecnológico." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/42/42132/tde-10052016-090949/.

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Os compostos de origem microbiana tem readquirido interesse pela biodisponibilidade, especificidade de alvo e diversidade química, mas as vias biosintéticas permanecem crípticas em condições de cultura. Uma estratégia para expressa-las é a super-expressão de genes ativadores. O laboratório de Bio-Produtos no ICB na USP tem trabalhado com Streptomyces olindensis produtor da Cosmomicina D uma molécula com atividade antitumoral de interesse devido ao padrão de glicosilação. O genoma de S. olindensis foi sequenciado e submetido ao NCBI (JJOH00000000) e utilizando o software antiSMASH foram identificados 33 clusters envolvidos na produção de metabolitos secundários. Encontraram-se clusters gênicos para a produção de metabolitos como Melanina, Geosmina, entre outros. Além, foi realizada uma analise de genômica comparativa para caracterizar e anotar as 22 vias biossintéticas desconhecidas em S. olindensis. Finalmente, escolheram-se a via do aminociclitol e um Policetídeo Tipo I para a super-expressão de genes reguladores levando a detecção do composto sob condições de cultura.
Microbial metabolites regain interest due to its bioavailability, target specificity and chemical diversity, but the biosynthetic pathways remain silenced under culture conditions. A strategy to obtain them is the over expression of regulatory genes. Bio-products laboratory at USP has been working with Streptomyces olindensis, products of Cosmomycin D, an antitumoral molecule with a distinctive glycosylation pattern. S. olindensis genome was sequenced and submitted to NCBI (JJOH00000000) and employing antiSMASH server 33 secondary metabolite related clusters were identified. Known pathways were found such as genes for melanin production, Geosmin and others. Additionally, a comparative genomic approach was used to characterize the 22 biosynthetic unknown pathways described in S. olindensis. Subsequently, Aminocyclitol and Polyketide Type I were chosen to evaluated, over expressing the regulatory genes, leading to the compound detection in regular culture conditions.
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Johansson, Karin. "Analysis of immunoglobulin gene expression focus on Oct2 /." Lund : Dept. of Cell and Molecular Biology, Lund University, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39776663.html.

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30

Siqueira, Débora Mathias de. "Estudo da correlação entre a expressão de genes reguladores do estado de hipóxia e a intensidade da resposta inflamatória aguda." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-07072009-114219/.

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A hipóxia ocorre quando a demanda de oxigênio molecular necessário para gerar ATP é insuficiente. Os genes ativados por hipóxia compreendem o gene Hif-1a (Hipóxia-fator induzível 1a), Vegf-a (fator de crescimento endotelial vascular a), Arnt e Vhl (von Hippel-Lindau). Neste estudo foram utilizadas linhagens de camundongos geneticamente selecionados para alta (AIRmax) ou baixa (AIRmin) resposta inflamatória aguda (AIR). Foram realizados testes biológicos para caracterizar as reações inflamatórias produzidas por Biogel e TPA, bem como o tipo PAH cancerígeno. Testamos a expressão de mRNA de genes de hipóxia e caracterização de polimorfismo da região codificadora do Hif-1a no cromossomo 12. Camundongos AIRmax demonstraram uma maior reação inflamatória que os AIRmin para biogel e TPA enquanto o inverso foi observado com o DMBA. Os conjuntos de dados de fenótipos, expressão gênica e polimorfismo candidatam a região do cromossomo 12, que contém, entre outros, o gene Hif-1a, como participante da regulação da AIR.
Hypoxia occurs when the demand for molecular oxygen necessary to generate ATP is insufficient. Genes activated by hypoxia comprise the Hif-1a gene (Hypoxia-Inducible Factor 1a), Vegf-a (Vascular Endothelial Growth Factor a), Arnt and Vhl (von Hippel-Lindau). In this study we used lines of mice genetically selected for high (AIRmax) or low (AIRmin) acute inflammatory response (AIR). We conducted biological tests to characterize the inflammatory reactions produced by Biogel and TPA, and the type PAH carcinogen. We tested the mRNA expression of genes of hypoxia and characterization of polymorphism of the coding region of Hif-1a gene on chromosome 12. We found that the mice AIRmax had greater intensity of the inflammatory reaction that AIRmin to biogel and TPA while the reverse was observed with the DMBA. The data sets of phenotypes, gene expression and polymorphism applying the region of chromosome 12 that contains, among others, the gene Hif-1a, as part of the regulation of AIR.
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31

Chan, Ping-kei. "The study of the regulatory elements of the human [beta]-globin gene." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31999062.

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32

Chan, Ping-kei, and 陳炳基. "The study of the regulatory elements of the human {221}-globin gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31999062.

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33

Karjalainen, Merja. "Analysing subsets of gene expression data to find putatively co-regulated genes." Thesis, University of Skövde, Department of Computer Science, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-712.

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This project is an investigation of whether analysing subsets of time series gene expression data can give additional information about putatively co-regulated genes, compared to only using the whole time series. The original gene expression data set was partitioned into subsets and similarity was computed for both the whole timed series and subsets. Pearson correlation was used as similarity measure between gene expression profiles. The results indicate that analysing co-expression in subsets of gene expression data derives true-positive connections, with respect to co-regulation, that are not detected by only using the whole time series data. Unfortunately, with the actual data set, chosen similarity measure and partitioning of the data, randomly generated connections have the same amount of true-positives as the ones derived by the applied analysis. However, it is worth to continue further analysis of the subsets of gene expression data, which is based on the multi-factorial nature of gene regulation. E.g. other similarity measures, data sets and ways of partitioning the data set should be tried.

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34

Camino, Eric M. "A Mechanistic Analysis of Gene Regulation and its Evolution in a Drosophila Model." University of Dayton / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1461242188.

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35

Spies, Noah (Noah Walter Benjamin). "Cross-regulation and interaction between eukaryotic gene regulatory processes." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72637.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis.
Includes bibliographical references.
Regulation of genes is fundamental to all living processes and can be exerted at many sequential steps. We studied several eukaryotic gene regulatory mechanisms with an emphasis on understanding the interplay between regulatory processes on a genome-wide scale. Gene splicing involves the joining of exonic RNA stretches from within a precursor messenger RNA (mRNA). Splicing typically occurs co-transcriptionally as the pre-mRNA is being produced from the DNA. We explored the relationship between the chromatin state of the gene-encoding DNA and the splicing machinery. We found a marked enrichment for nucleosomes at exonic DNA in human T cells, as compared to surrounding introns, an effect mostly explained by the biased nucleotide content of exons. The use of nucleosome positioning information improved splicing simulation models, suggesting nucleosome positioning may help determine cellular splicing patterns. Additionally, we found several histone marks enriched or depleted at exons compared to the background nucleosome levels, indicative of a histone code for splicing. These results connect the chromatin regulation and mRNA splicing processes in a genome-wide fashion. Another pre-mRNA processing step is cleavage and polyadenylation, which determines the 30 end of the mature mRNA. We found that 3P-Seq was able to quantify the levels of 30 end isoforms, in addition to the method's previous use for annotating mRNA 30 ends. Using 3P-Seq and a transcriptional shutoff experiment in mouse fibroblasts, we investigated the e?effect of nuclear alternative 30 end formation on mRNA stability, typically regulated in the cytoplasm. In genes with multiple, tandem 30 untranslated regions (30 UTRs) produced by alternative cleavage and polyadenylation, we found the shorter UTRs were significantly more stable in general than the longer isoforms. This di?difference was in part explained by the loss of cis-regulatory motifs, such as microRNA targets and PUF-binding sites, between the proximal and distal isoforms. Finally, we characterized the small interfering RNAs (siRNAs) produced from heterochromatic, silenced genomic regions in fission yeast. We observed a considerable bias for siRNAs with a 5' U, and used this bias to infer patterns of siRNA biogenesis. Furthermore, comparisons with between wild-type and the Cid14 non-canonical poly(A) polymerase mutant demonstrated that the exosome, the nuclear surveillance and processing complex, is required for RNA homeostasis. In the absence of a fully functional exosome complex, siRNAs are produced to normal exosome targets, including ribosomal and transfer RNAs, indicating these processes may compete for substrates and underscoring the interconnectedness of gene regulatory systems.
by Noah Spies.
Ph.D.
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36

Shah, Supriya A. "Determination of Rx expression in the adult mouse retina and delineation of the Rx mediated gene regulation." Morgantown, W. Va. : [West Virginia University Libraries], 2005. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4080.

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Thesis (M.S.)--West Virginia University, 2005.
Title from document title page. Document formatted into pages; contains viii, 99 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 82-99).
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37

Garstang, Myles Grant. "The evolution and regulation of the chordate ParaHox cluster." Thesis, University of St Andrews, 2016. http://hdl.handle.net/10023/11788.

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The ParaHox cluster is the evolutionary sister of the Hox cluster. Like the Hox cluster, the ParaHox cluster is subject to complex regulatory phenomena such as collinearity. Despite the breakup of the ParaHox cluster within many animals, intact and collinear clusters have now been discovered within the chordate phyla in amphioxus and the vertebrates, and more recently within the hemichordates and echinoderms. The archetypal ParaHox cluster of amphioxus places it in a unique position in which to examine the regulatory mechanisms controlling ParaHox gene expression within the last common ancestor of chordates, and perhaps even the wider Deuterostomia. In this thesis, the genomic and regulatory landscape of the amphioxus ParaHox cluster is characterised in detail. New genomic and transcriptomic resources are used to better characterise the B.floridae ParaHox cluster and surrounding genomic region, and conserved non-coding regions and regulatory motifs are identified across the ParaHox cluster of three species of amphioxus. In conjunction with this, the impact of retrotransposition upon the ParaHox cluster is examined and analyses of transposable elements and the AmphiSCP1 retrogene reveal that the ParaHox cluster may be more insulated from outside influence than previously thought. Finally, the detailed analyses of a regulatory element upstream of AmphiGsx reveals conserved mechanisms regulating Gsx CNS expression within the chordates, and TCF/Lef is likely a direct regulator of AmphiGsx within the CNS. The work in this thesis makes use of new genomic and transcriptomic resources available for amphioxus to better characterise the genomic and regulatory landscape of the amphioxus ParaHox cluster, serving as a basis for the improved identification and characterisation of functional regulatory elements and conserved regulatory mechanisms. This work also highlights the potential of Ciona intestinalis as a ‘living test tube' to allow the detailed characterisation of amphioxus ParaHox regulatory elements.
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Hughes, Thomas. "The genetic regulation of Kranz anatomy in maize." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:86184e64-c7bb-43e9-9320-0ebbb2793ea8.

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The C4 photosynthetic pathway acts to concentrate CO2 around the enzyme Ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco), ensuring that it catalyses a carboxylation rather than oxygenation reaction, which in turn suppresses photorespiration. In nearly all cases C4 photosynthesis is underpinned by characteristic Kranz anatomy, with concentric wreaths of bundle sheath (BS) and mesophyll (M) cells surrounding closely spaced veins. The increased yields associated with the C4 pathway have lead to the suggestion that C3 crops such as rice should be engineered to undertake C4 photosynthesis, however, this goal is currently held back by a lack of understanding about how the development of Kranz anatomy is regulated. Recently, a number of candidate Kranz regulators have been identified in an RNA-seq study that compared leaf development in maize foliar (Kranz) and husk (non-Kranz) leaves. However, this study did not consider the impact of a recent whole genome duplication in the maize lineage on the gene expression patterns analysed. Therefore, in this thesis maize homeolog gene-pair divergence during early leaf development was assessed. This revealed that expression divergence of homeolog gene-pairs is a significant evolutionary phenomenon. Functional validation of a subset of Kranz candidates revealed that a Zmscr1-1; Zmscr1h-1 double mutant exhibited defects in Kranz patterning, including increased formation of extra BS cells and veins with no separating M cells. Furthermore, Zmnkd1; Zmnkd2 double mutants exhibited a subtle increase in extra BS cell formation. Taken together, this indicates that both ZmSCR1/ZmSCR1h and ZmNKD1/ZmNKD2 function redundantly during Kranz development. No evidence was obtained that two additional genes, ZmSHR2 and ZmRVN1, play a role in Kranz development, and expression of candidate Kranz regulators in rice did not alter leaf anatomy. Together, this work has confirmed roles for a number of genes in Kranz regulation, and has provided insight into the complex regulation underpinning Kranz development in maize.
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39

Montgomery, Stephen. "On computational strategies for regulatory element and regulatory polymorphism detection." Thesis, University of British Columbia, 2006. http://hdl.handle.net/2429/58.

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Identification of the mechanisms by which genes are regulated in eukaryotes is one of the principal challenges of modern biology. The emergence of genome sequencing has facilitated the marked expansion of experimental and computational approaches designed to address this challenge. Integrating and assessing this information remains a major scientific endeavor that requires new and innovative application of technology. Furthermore, our limited understanding of the mechanisms of gene regulation in eukaryotes has undermined our ability to understand the role of genetics in gene regulation. Regulatory variants are thought to be responsible for a considerable amount of the heterogeneity within our population and to be fundamental determinants of health. New experimental approaches offer the opportunity to effectively identify markers of disease susceptibility in gene regulatory regions but the discovery of the molecular mechanism of dysregulation remains difficult and time-consuming. It is here where computational approaches are required to prioritize candidate regulatory variants. To do so requires the development of an extensive control set from which characteristic signals can be identified. This thesis introduces novel approaches for discovering, utilizing, comparing and visualizing regulatory element predictions in completed genomes. This thesis also introduces novel bioinformatics infrastructure for curating regulatory element and variant datasets, and introduces the largest-available, open-access dataset of functional regulatory variants hand-curated from literature. This dataset is used to identify signals which discriminate functional variants from other variants in the promoter regions of human genes using regulatory and population genetics-based computational approaches.
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40

Hong, Ted. "Alteration of Human Gene Regulatory Networks by Human Virus Transcriptional Regulators." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1593273403439508.

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41

Blanding, Carletha R. "Maize gene expression UV response patterns reveal coordinate regulation of many genes /." Electronic version (Microsoft Word), 2005. http://dl.uncw.edu/etd/2005/blandingc/carlethablanding.doc.

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42

Pati, Amrita. "Modeling and Analysis of Regulatory Elements in Arabidopsis thaliana from Annotated Genomes and Gene Expression Data." Thesis, Virginia Tech, 2005. http://hdl.handle.net/10919/44132.

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Modeling of cis-elements in the upstream regions of genes is a challenging computational problem. A set of regulatory motifs present in the promoters of a set of genes can be modeled by a biclique. Combinations of cis-elements play a vital role in ascertaining that the correct co-action of transcription factors binding to the gene promoter, results in appropriate gene expression in response to various stimuli. Geometrical and spatial constraints in transcription factor binding also impose restrictions on order and separation of cis-elements. Not all regulatory elements that coexist are biologically significant. If the set of genes in which a set of regulatory elements co-occur, are tightly correlated with respect to gene expression data over a set of treatments, the regulatory element combination can be biologically directed. The system developed in this work, XcisClique, consists of a comprehensive infrastructure for annotated genome and gene expression data for Arabidopsis thaliana. XcisClique models cis-regulatory elements as regular expressions and detects maximal bicliques of genes and motifs, called itemsets. An itemset consists of a set of genes (called a geneset) and a set of motifs (called a motifset) such that every motif in the motifset occurs in the promoter of every gene in the geneset. XcisClique differs from existing tools of the same kind in that, it offers a common platform for the integration of sequence and gene expression data. Itemsets identified by XcisClique are not only evaluated for statistical over-representation in sequence data, but are also examined with respect to the expression patterns of the corresponding geneset. Thus, the results produced are biologically directed. XcisClique is also the only tool of its kind for Arabidopsis thaliana, and can also be used for other organisms in the presence of appropriate sequence, expression, and regulatory element data. The web-interface to a subset of functionalities, source code and supplemental material are available online at http://bioinformatics.cs.vt.edu/xcisclique.
Master of Science
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43

Lee, Hing-leung Eric, and 李慶亮. "Genetic and epigenetic factors controlling the expression of sialyltransferase gene ST6GAL1." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B4150849X.

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44

Lee, Hing-leung Eric. "Genetic and epigenetic factors controlling the expression of sialyltransferase gene ST6GAL1." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B4150849X.

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45

Guimbellot, Jennifer S. "Role of hypoxia in epithelial gene regulation." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/guimbellot.pdf.

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46

Andersson, Malin. "A method for identification of putatively co-regulated genes." Thesis, University of Skövde, Department of Computer Science, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-705.

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The genomes of several organisms have been sequenced and the need for methods to analyse the data is growing. In this project a method is described that tries to identify co-regulated genes. The method identifies transcription factor binding sites, documented in TRANSFAC, in the non-coding regions of genes. The algorithm counts the number of common binding sites and the number of unique binding sites for each pair of genes and decides if the genes are co-regulated. The result of the method is compared with the correlation between the gene expression patterns of the genes. The method is tested on 21 gene pairs from the genome of Saccharomyces cerevisiae. The algorithm first identified binding sites from all organisms. The accuracy of the program was very low in this case. When the algorithm was modified to only identify binding sites found in plants the accuracy was much improved, from 52% to 76% correct predictions.

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47

Belcastro, Vincenzo. "Reverse engieering gene regulatory networks : Elucidation of trancriptome organization, gene function and gene regulation in mammalian systems." Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534377.

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48

Furchtgott, Leon A. "Simultaneous Inference of Cell Types, Lineage Trees, and Regulatory Genes From Gene Expression Data." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493563.

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Important goals of developmental biology include identifying cell types, understanding the sequence of lineage choices made by multipotent cells and unconvering the molecular networks controlling these decisions. Achieving these goals through computational analysis of gene expression data has been difficult. In this dissertation supervised by Sharad Ramanathan, I develop a probabilistic framework to identify cell types, infer lineage relationships and discover core gene networks controlling lineage decisions. Working with Sandeep Choubey and Sumin Jang, we infer the gene expression dynamics of early differentiation of mouse embryonic stem cells, revealing discrete state transitions across nine cell states. Using a probabilistic model of the gene regulatory networks, we predict that these states are further defined by distinct responses to perturbations and experimentally verify three such examples of state-dependent behavior. Working with Vilas Menon and Sam Melton, we infer a lineage tree for early neural development and putative regulatory transcription factors from single-cell transcriptomic profiles. The lineage tree shows a prominent bifurcation between cortical and mid/hindbrain cell types, and the inferred lineage relationships were confirmed by clonal analysis experiments. In summary, this study provides a framework to infer predictive models of the gene regulatory networks that drive cell fate decisions.
Biophysics
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Singh, Anish D. "Regulation and function of the non-muscle [beta]-actin and [gamma]-actin genes." Phd thesis, Department of Paediatrics and Child Health, Faculty of Medicine, 2004. http://hdl.handle.net/2123/11556.

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50

Khoyratty, Tariq. "Interferon regulatory factor 5 : a systematic study of macrophage gene regulation." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:b820f612-ceb7-4e2c-af26-52999e368c41.

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Abstract:
Macrophages are multifaceted innate immune cells, able to adapt their phenotype to respond to a myriad of conditions, engaging in tissue-specific functions and mediating either inflammatory or anti-inflammatory responses depending on the encountered stimuli. They conduct key roles in the orchestration of immune responses; from pathogen recognition through sterilising inflammation to resolution and repair. The Udalova laboratory has previously demonstrated that IRF5 promotes a pro- inflammatory macrophage phenotype, leading to the secretion of TNF, IL-12, and IL-23, enhancing Th1/Th17-mediated immune responses, and described the cooperation between IRF5 and the transcription factor RelA, which mediate the production of pro-inflammatory genes. The aim of this thesis is to further characterise the activity of IRF5 in macrophage inflammatory responses. I demonstrate that IRF5 not only regulates the transcription of cytokines and chemokines in response to bacterial stimuli, but also anti-microbial peptides, whilst simultaneously down-regulating homeostatic and resolving macrophage functions. My data also suggests that IRF5 plays a role in enforcing monocyte to macrophage differentiation by up-regulating the transcription of key macrophages markers and repressing dendritic cell identity genes. To further characterise the mechanisms of the inflammatory response mounted by macrophages I used an unbiased approach; combining twenty-three transcription factor ChIP-seq data sets with chromatin accessibility information from ATAC-seq, uncovering RUNX1 as a novel partner of IRF5 that binds co-operatively to clusters of enhancers, which control the transcription of pro-inflammatory genes in a signal-dependent manner. This is the first study demonstrating a critical role for RUNX1 in activity of inflammatory macrophages.
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