Dissertations / Theses: 'Leukemic Gene Expression Regulation'

1

Kuchinskaya, Ekaterina. "Genetic studies of acute lymphoblastic leukemia /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-337-5/.

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2

Lok, Chun-nam, and 陸振南. "Regulation of transferrin receptor expression in human leukemic HL-60 cells: gene expression and cellular signaling." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31235141.

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3

Lok, Chun-nam. "Regulation of transferrin receptor expression in human leukemic HL-60 cells : gene expression and cellular signaling /." Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17310659.

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4

Roos, Cecilia. "Studies of leukotriene C4 synthase expression and regulation in chronic myeloid leukaemia /." Karlstad : Faculty of Technology and Science, Biomedical Science, Karlstads universitet, 2008. http://www.diva-portal.org/kau/abstract.xsql?dbid=1598.

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5

Fält, Susann. "Analysis of global gene expression in complex biological systems using microarray technology /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-612-3/.

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6

Schiemann, William Paul. "Determination and characterization of leukemia inhibitory factor receptor signal transduction systems /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/6277.

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7

Xue, Liting. "Oncogene Function in Pre-Leukemia Stage of INV(16) Acute Myeloid Leukemia: A Dissertation." eScholarship@UMMS, 2010. http://escholarship.umassmed.edu/gsbs_diss/740.

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The CBFbeta-SMMHC fusion protein is expressed in acute myeloid leukemia (AML) samples with the chromosome inversion inv(16)(p13;q22). This fusion protein binds the transcription factor RUNX with higher affinity than its physiological partner CBFbeta and disrupts the core binding factor (CBF) activity in hematopoietic stem and progenitor cells. Studies in the Castilla laboratory have shown that CBFbeta-SMMHC expression blocks differentiation of hematopoietic progenitors, creating a pre-leukemic progenitor that progresses to AML in cooperation with other mutations. However, the combined function of cumulative cooperating mutations in the pre-leukemic progenitor cells that enhance their expansion to induce leukemia is not known. The standard treatment for inv(16) AML is based on the use of non-selective cytotoxic chemotherapy, resulting in a good initial response, but with limited long-term survival. Therefore, there is a need for developing targeted therapies with improved efficacy in leukemic cells and minimal toxicity for normal cells. Here, we used conditional Nras+/LSL-G12D; Cbfb+/56M; Mx1Cre knock-in mice to show that allelic expression of oncogenic N-RasG12D expanded the multi-potential progenitor (MPP) compartment by 8 fold. Allelic expression of Cbfbeta-SMMHC increased the MPPs and short-term hematopoietic stem cells (ST-HSCs) by 2 to 4 fold both alone and in combination with N-RasG12D expression. In addition, allelic expression of oncogenic N-RasG12D and Cbfbeta-SMMHC increases survival of pre-leukemic stem and progenitor cells. Differential analysis of bone marrow cells determined that Cbfb+/MYH11 and Nras+/G12D; vii Cbfb+/MYH11 cells included increased number of blasts, myeloblasts and promyelocytes and a reduction in immature granulocytes, suggesting that expression of N-RasG12D cannot bypass Cbfbeta-SMMHC driven differentiation block. N-RasG12D and Cbfbeta-SMMHC synergized in leukemia, in which Nras+/G12D; Cbfb+/MYH11 mice have a shorter median latency than Cbfb+/MYH11 mice. In addition, the synergy in leukemogenesis was cell autonomous. Notably, leukemic cells expressing N-RasG12D and Cbfbeta-SMMHC showed higher (over 100 fold) leukemia-initiating cell activity in vivo than leukemic cells expressing Cbfbeta-SMMHC (L-IC activity of 1/4,000 and 1/528,334, respectively). Short term culture and biochemical assays revealed that pre-leukemic and leukemic cells expressing N-RasG12D and Cbfbeta-SMMHC have reduced levels of pro-apoptotic protein Bim compared to control. The Nras+/G12D; CbfbMYH11 pre-leukemic and leukemic cells were sensitive to pharmacologic inhibition of MEK/ERK signaling pathway with increasing apoptosis and Bim protein levels but not sensitive to PI3K inhibitors. In addition, knock-down of Bcl2l11 (Bim) expression in Cbfbeta-SMMHC pre-leukemic progenitors decreased their apoptosis levels. In collaboration with Dr. John Bushweller’s and other research laboratories, we recently developed a CBFbeta-SMMHC inhibitor named AI-10-49, which specifically binds to CBFbeta-SMMHC, prevents its binding to RUNX proteins and restores CBF function. Biochemical analysis in human leukemic cells showed that AI-10-49 has significant specificity in reducing the viability of leukemic cells expressing CBFbeta-SMMHC (IC50= 0.83μM), and negligible toxicity in normal cells. Likewise, mouse Nras+/G12D; viii Cbfb+/MYH11 leukemic cells were sensitive to AI-10-49 (IC50= 0.93μM). By using the NrasLSL-G12D; Cbfb56M mouse model, we also show that AI-10-49 significantly prolongs the survival of mice bearing the leukemic cells. Preliminary mechanistic analysis of AI-10-49 activity has shown that AI-10-49 increased BCL2L11 transcript levels in a dose and time dependent manner in murine and human leukemic cells, suggesting that the viability through BIM-mediated apoptosis may be targeted by both oncogenic signals. My thesis study demonstrates that Cbfbeta-SMMHC and N-RasG12D promote the survival of pre-leukemic myeloid progenitors primed for leukemia by activation of the MEK/ERK/Bim axis, and define NrasLSL-G12D; Cbfb56M mice as a valuable genetic model for the study of inv(16) AML targeted therapies. For instance, the novel CBFbeta-SMMHC inhibitor AI-10-49 shows a significant efficacy in this mouse model. This small molecule will serve as a promising first generation drug for targeted therapy of inv(16) leukemia and also a very useful tool to understand mechanisms of leukemogenesis driving by CBFbeta-SMMHC.

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8

Xue, Liting. "Oncogene Function in Pre-Leukemia Stage of INV(16) Acute Myeloid Leukemia: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/740.

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Abstract:

The CBFbeta-SMMHC fusion protein is expressed in acute myeloid leukemia (AML) samples with the chromosome inversion inv(16)(p13;q22). This fusion protein binds the transcription factor RUNX with higher affinity than its physiological partner CBFbeta and disrupts the core binding factor (CBF) activity in hematopoietic stem and progenitor cells. Studies in the Castilla laboratory have shown that CBFbeta-SMMHC expression blocks differentiation of hematopoietic progenitors, creating a pre-leukemic progenitor that progresses to AML in cooperation with other mutations. However, the combined function of cumulative cooperating mutations in the pre-leukemic progenitor cells that enhance their expansion to induce leukemia is not known. The standard treatment for inv(16) AML is based on the use of non-selective cytotoxic chemotherapy, resulting in a good initial response, but with limited long-term survival. Therefore, there is a need for developing targeted therapies with improved efficacy in leukemic cells and minimal toxicity for normal cells. Here, we used conditional Nras+/LSL-G12D; Cbfb+/56M; Mx1Cre knock-in mice to show that allelic expression of oncogenic N-RasG12D expanded the multi-potential progenitor (MPP) compartment by 8 fold. Allelic expression of Cbfbeta-SMMHC increased the MPPs and short-term hematopoietic stem cells (ST-HSCs) by 2 to 4 fold both alone and in combination with N-RasG12D expression. In addition, allelic expression of oncogenic N-RasG12D and Cbfbeta-SMMHC increases survival of pre-leukemic stem and progenitor cells. Differential analysis of bone marrow cells determined that Cbfb+/MYH11 and Nras+/G12D; vii Cbfb+/MYH11 cells included increased number of blasts, myeloblasts and promyelocytes and a reduction in immature granulocytes, suggesting that expression of N-RasG12D cannot bypass Cbfbeta-SMMHC driven differentiation block. N-RasG12D and Cbfbeta-SMMHC synergized in leukemia, in which Nras+/G12D; Cbfb+/MYH11 mice have a shorter median latency than Cbfb+/MYH11 mice. In addition, the synergy in leukemogenesis was cell autonomous. Notably, leukemic cells expressing N-RasG12D and Cbfbeta-SMMHC showed higher (over 100 fold) leukemia-initiating cell activity in vivo than leukemic cells expressing Cbfbeta-SMMHC (L-IC activity of 1/4,000 and 1/528,334, respectively). Short term culture and biochemical assays revealed that pre-leukemic and leukemic cells expressing N-RasG12D and Cbfbeta-SMMHC have reduced levels of pro-apoptotic protein Bim compared to control. The Nras+/G12D; CbfbMYH11 pre-leukemic and leukemic cells were sensitive to pharmacologic inhibition of MEK/ERK signaling pathway with increasing apoptosis and Bim protein levels but not sensitive to PI3K inhibitors. In addition, knock-down of Bcl2l11 (Bim) expression in Cbfbeta-SMMHC pre-leukemic progenitors decreased their apoptosis levels. In collaboration with Dr. John Bushweller’s and other research laboratories, we recently developed a CBFbeta-SMMHC inhibitor named AI-10-49, which specifically binds to CBFbeta-SMMHC, prevents its binding to RUNX proteins and restores CBF function. Biochemical analysis in human leukemic cells showed that AI-10-49 has significant specificity in reducing the viability of leukemic cells expressing CBFbeta-SMMHC (IC50= 0.83μM), and negligible toxicity in normal cells. Likewise, mouse Nras+/G12D; viii Cbfb+/MYH11 leukemic cells were sensitive to AI-10-49 (IC50= 0.93μM). By using the NrasLSL-G12D; Cbfb56M mouse model, we also show that AI-10-49 significantly prolongs the survival of mice bearing the leukemic cells. Preliminary mechanistic analysis of AI-10-49 activity has shown that AI-10-49 increased BCL2L11 transcript levels in a dose and time dependent manner in murine and human leukemic cells, suggesting that the viability through BIM-mediated apoptosis may be targeted by both oncogenic signals. My thesis study demonstrates that Cbfbeta-SMMHC and N-RasG12D promote the survival of pre-leukemic myeloid progenitors primed for leukemia by activation of the MEK/ERK/Bim axis, and define NrasLSL-G12D; Cbfb56M mice as a valuable genetic model for the study of inv(16) AML targeted therapies. For instance, the novel CBFbeta-SMMHC inhibitor AI-10-49 shows a significant efficacy in this mouse model. This small molecule will serve as a promising first generation drug for targeted therapy of inv(16) leukemia and also a very useful tool to understand mechanisms of leukemogenesis driving by CBFbeta-SMMHC.

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9

Bartoe, Joseph L. "The regulation of LIF- and CNTF-mediated signal transduction /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/6256.

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10

Fan, Kin-pong, and 范健邦. "The expression, regulation and functional role of SOX7 gene in acute myeloid leukemia." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45902914.

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11

Istook, Diana Lee. "Differential gene expression between patients with acute lymphocytic leukemia and patients with acute myeloid leukemia : the use of analysis of variance models in microarray data analysis /." Oklahoma City : [s.n.], 2004.

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12

Sullivan, Amy Lynn. "Regulation of gene expression programs by serum response factor and megakaryoblastic leukemia 1/2 in macrophages." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3386598.

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Thesis (Ph. D.)--University of California, San Diego, 2009.
Title from first page of PDF file (viewed Jan. 14, 2010). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 97-114).

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13

Dimberg, Anna. "The role of Stat 1 in retinoic acid-induced myelomonocytic differentiation of human leukemia cells /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5224-8/.

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14

Ong, Colin Heng Piew 1968. "Characterization of granulin gene expression in wounds and myelogenous leukemic cells." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86070.

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Progranulin (PC-cell derived growth factor, acrogranin, granulin-epithelin precursor) is a secreted glycoprotein with growth promoting activities for diverse cell types and is the precursor for the 6 kDa granulin peptides. These peptides were initially identified in inflammatory cells i.e. neutrophils; and this led to the hypothesis that the grn(granulin ) gene and its products may be regulated during, and function in, wound repair. In response to tissue injury, the grn gene is induced in endothelial cells and fibroblasts. Expression was observed in epithelial and inflammatory cells with higher expression in the inflammatory cells in the early phases of wound healing. This is the first evidence that demonstrates grn gene regulation in an adult physiological state. Given the high expression of the grn gene in hematopoietic cells, particularly the cells of the myeloid lineage, and that these cells are a source of granulin peptides, it was important to understand the signals that regulate progranulin transcript levels in these cells. For this investigation, two myelogenous cell lines, U937 (human histiocytic lymphoma) and HL-60 (human promyelocytic), which are models for monocytic and granulocytic maturation were chosen. Both these lineage related cell lines displayed differential regulation of the progranulin mRNA. The two cell lines were responsive to all three of the differentiation agents, investigated; all-trans retinoic acid (ATRA), dimethylsulphoxide (DMSO) and phorbol-12-myristate-13-acetate (PMA) with the exception of PMA-treated HL-60 cells which exhibit no change in the progranulin transcript levels. As differentiation occurs, the levels of progranulin transcript are up-regulated. However, progranulin does not stimulate the differentiation of these cells as assessed by the expression of the surface marker, CD11b which suggests that the increased levels of progranulin transcript is likely to be a characteristic of matured cells (inf

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15

Carvalho, Daniel Diniz de. "Regulação da expressão de SH3BGRL2, D53, PRAME, DAP12 e calcineurina A beta por BCR-ABL e consequências biológicas dessa regulação na LMC." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-03022010-091640/.

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Sabe-se que TRAIL é capaz de matar células tumorais de forma seletiva e que TRAIL tem sua expressão reduzida em diversos tumores, porém pouco se sabe sobre os mecanismos responsáveis pela sua inibição. Tendo em vista que a expressão de TRAIL pode ser regulada pelo Ácido Retinóico; que PRAME é capaz de inibir a via do ácido retinóico através da proteína EZH2 e que nós observamos anteriormente que a expressão de TRAIL esta diminuída em pacientes com LMC, nós decidimos investigar a associação entre PRAME, EZH2 e TRAIL na LMC. Nós demonstramos que PRAME, mas não EZH2, tem sua expressão aumentada em células BCR-ABL+ e sua expressão está associada com a progressão da LMC. Alem disto, existe uma correlação positiva entre PRAME e BCR-ABL e negativa entre PRAME e TRAIL nestes pacientes. A inibição da expressão de PRAME ou EZH2 por RNAi induziu um aumento da expressão de TRAIL. Estes dados revelam um novo mecanismo de regulação responsável por diminuir a expressão de TRAIL, e geram novos possíveis alvos para a terapia da LMC e, possivelmente, também para outros tumores.
TRAIL was shown to selectively kill tumor cells. Not surprisingly, TRAIL is down-regulated in a variety of tumor cells, but the mechanism responsible for TRAIL inhibition remains elusive. Because TRAIL can be regulate by retinoic acid; PRAME was shown to inhibit transcription of retinoic acid receptor target genes through the polycomb protein EZH2; and we have found that TRAIL is inversely correlated with BCR-ABL in CML patients, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is up-regulated in BCR-ABL cells and is associated with the progression of disease in CML patients. In addition, PRAME expression is positively correlated with BCR-ABL and negatively with TRAIL in these patients. Importantly, knocking down of PRAME or EZH2 by RNA interference restores TRAIL expression. Our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML.

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16

McGillivray, Shauna Marie. "Regulation of gonadotrope gene expression /." Diss., Connect to a 24 p. preview or request complete full text in PDF formate. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3208634.

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17

Palm, Kaia. "Regulation of neuronal gene expression /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980612palm.

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18

Mason, J. O. "Regulation of immunoglobulin gene expression." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384506.

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19

Ebert, Benjamin L. "Oxygen regulation of gene expression." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296895.

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20

Collier, William. "Gene expression regulation in Pneumoviruses." Thesis, University of Warwick, 2017. http://wrap.warwick.ac.uk/102038/.

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Members of the Pneumoviridae virus family are responsible for severe respiratory tract disease in their hosts. Human respiratory syncytial virus (hRSV) is responsible for over 200,000 deaths worldwide each year and bovine respiratory syncytial virus (bRSV) causes major economic loss to the cattle industry worldwide. The current model for all nonsegmented negative-sense single stranded RNA virus gene expression, is that mRNA is generated in a polar gradient, with decreasing levels of mRNA transcribed from genes further along the genome from the 3 ́ end. With the exception of translation of ORF-2 located on the bicistronic M2 mRNA, translation of Pneumoviridae mRNAs is thought to be regulated through the levels of mRNA abundance. Translation of M2 ORF-2 has been characterised as being regulated by the non-canonical mechanism of coupled translation termination/initiation in pneumonia virus of mice (PVM), hRSV and avian metapneumovirus (APV). This mechanism is reliant on a proportion of the elongating ribosome translating the upstream M2 ORF-1, terminating and reinitiating translation of M2 ORF-2. Although the initiation site for M2 ORF-2 is similar in bRSV to other members of this family that use the mechanism of coupled translation, the mechanism has not been characterised. Using the technique of ribosomal profiling to analyse steady state viral mRNA abundance and viral translation in both hRSV and bRSV-infected cells, it was observed that for certain viral mRNAs, levels of mRNA abundance did not follow the standard polar transcription model. This was characterised by an increase in the levels of mRNA abundance between the mRNA’s respective gene and its upstream neighbour. The increase was observed in the same group of mRNAs in both viruses suggesting that factors other than the transcription polar gradient influence levels of viral mRNA abundance. It was also observed that levels of proportional translation did not match the respective proportional levels of mRNA abundance for certain viral mRNAs in both viruses. This would suggest that translation of viral genomes is not primarily controlled by mRNA abundance and instead other translational regulatory factors influence levels of translation. The mechanism of bRSV M2 ORF-2 translation was also characterised using reporter plasmids assays. It was identified that the mechanism of initiation of translation of M2 ORF2 used, was not that of coupled translation termination/initiation used by other members of this family. Instead it was observed that translation of M2 ORF-2 used an internal initiation mechanism located inside M2 ORF-1 to initiate translation. The mechanism of coupled translation termination/initiation used for translation of PVM M2 ORF-2 was also further characterised. It was observed that translation of M2 ORF-2 was reliant on upstream sequence in the M2 ORF-1 sequence. A predicted mRNA secondary structure was identified in this region and when disrupted, inhibited translation of M2 ORF2. This was similar to the mechanism of coupled translation used in hRSV, suggesting that the mechanism used by this family is reliant on a mRNA secondary structure located upstream of the initiation site.

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21

Heur, J. Martin. "Lysosomal Regulation of Gene Expression." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1026512116.

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22

Bewry, Nadine N. "STAT3 Contributes to Resistance Towards BCR-ABL Inhibitors in a Bone Marrow Microenvironment Model of Drug Resistance in Chronic Myeloid Leukemia Cells." [Tampa, Fla] : University of South Florida, 2009. http://purl.fcla.edu/usf/dc/et/SFE0002892.

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23

Chan, Yvonne. "Epigenetic regulation of enos gene expression." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0012/MQ40769.pdf.

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24

Dalton, Stephen. "Transcriptional regulation of histone gene expression /." Title page, contents and summary only, 1987. http://web4.library.adelaide.edu.au/theses/09PH/09phd152.pdf.

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25

Clements, Andrew R. N. "The regulation of globin gene expression." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365687.

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26

Campbell, Paul L. "Regulation of human globin gene expression." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276524.

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27

Santoro, Emilio. "Regulation of gene expression by microRNAs." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546591.

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28

White, Peter. "Nutritional regulation of muscle gene expression." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624160.

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29

Kelly, Steven Bryan. "Regulation of gene expression in trypanosomes." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496987.

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30

Hadingham, Sophie Anne. "Sugar-regulation of plant gene expression." Thesis, University of East Anglia, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410132.

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31

Tigue, P. J. "Hormonal regulation of mammary gene expression." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381461.

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32

Kowalczyk, Anna M. "The regulation of HPV gene expression." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424404.

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33

Head, Mark William. "The regulation of crystallin gene expression." Thesis, University of Edinburgh, 1991. http://hdl.handle.net/1842/14037.

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The crystallins are the super-abundant structural proteins of vertebrate lens fibre cells, but certain of the crystallins are found at very much lower levels in some non-lens tissues. Chick α-, β and δ-crystallins are each encoded by a multi-gene family and their expression is developmentally regulated resulting in the changing pattern of crystallin composition of the successively formed lens fibre cells. The presence of α-, β- and δ-crystallins in extralenticular chick tissues, including the retina, is examined here at the level of individual crystallin RNAs by Northern, dot-blot and in situ hybridisation, and the accumulated crystallin polypeptides are examined by Western blotting and immunohistochemistry. αA-crystallin, several β-crystallins and both δ1 and δ2-crystallins are found to be expressed in non-lens chick tissues and the quantitative balance of δ-crystallin and individual β-crystallin polypeptides in non-lens tissues is found to be tissue-specific. The relative steady-stage levels of δ1- and δ2-crystallin mRNA are found to differ between lens and non-lens tissue and to be effected by transcriptional and post-transcriptional mechanisms. Selective inhibition of αA-crystallin synthesis using antisense oligonucleotides in vitro shows that αA-crystallin appears to be required for the correct differentiation of both developing lens and retina. The pattern of α-, β- and δ-crystallin expression in non-lens tissues is interpreted in terms of the possible status of crystallins as multifunctional proteins and is used to question current theories concerning the evolutionary origin, expression and current functions of these proteins.

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34

Fischer, Heléne. "Gene expression in carcinogenesis /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4961-1/.

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35

Sasmono, R. Tedjo. "Transcriptional regulation of c-fms gene expression /." [St. Lucia, Qld.], 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17479.pdf.

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36

Gaasenbeek, Michelle Lynn. "Regulation of non-pituitary prolactin gene expression." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ32480.pdf.

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37

Moulin, Danielle S. "Regulation of expression of the CFTR gene." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298347.

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Gleadle, Jonathan M. "Regulation of mammalian gene expression by oxygen." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360257.

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39

Jagannathan, Aparna. "Regulation of gene expression in Campylocacter jejuni." Thesis, University of Birmingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397575.

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The flagellum of Campy/obaeter jejuni is a major virulence determinant, dependent on about 40 flagellar genes that are co-ordinately expressed. However, the existence of a flagellar regulon in C. jejuni and the genes that may control it are so far undefined. To elucidate this, three putative global regulatory gene homologues, rpoN, fliA and flgR encoding the alternative sigma factors, 0'54, 0'28 and the 0'54 -associated transcriptional activator FlgR respectively, were selected. The genes were cloned and mutated by inverse PCR mutagenesis. Kanamycin resistant mutants were constructed by allelic replacement in two C. jejuni strains, NCTC 11168 and NCTC 11828. Electron microscopic studies showed that the rpoN and flgR mutants were nonflagellate; the fliA mutant had truncated flagella. Immunoblotting confirmed lack of flagellin expression in the rpoN and flgR mutants and partial flagellin expression in the fliA mutant. Thus neither the flaB gene with a 0'54 promoter encoding the minor flagellin, nor the flaA gene with a 0'28 promoter encoding the major flagellin are expressed in the rpoN andflgR mutants. These observations confirm the roles of rpoN,flgR andfliA gene homologues in flagellar expression in C.jejuni. Promoter analysis of all the flagellar genes in C. jejuni shows that rpoN and flgR are essential regulatory genes in the putative flagellar regulon of C. jejuni. Microarray hybridisations and analyses reveal that mutation of the rpoN and/or flgR genes affects regulation of expression of several flagellar genes. These analyses shed light on the distinct difference in flagellar regulon between enteric bacteria and C. jejuni and outline the flagellar regulon of the latter. Studies were also carried out with two putative flagellar regulatory genes, Inr and regX3. However, mutations in these genes did not affect the nature of the flagella.

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40

Eaton, Tracy Jayne. "Regulation of gene expression in Lactococcus lactis." Thesis, University of East Anglia, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359937.

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41

Purton, M. E. "Regulation of gene expression during tomato ripening." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378485.

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42

Elia, Andrew Panayioti. "Tissue specific regulation of CYP2B gene expression." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338734.

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43

Malik, Bilal. "Regulation of gene expression in Alzheimer's disease." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423256.

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Sesto, Nina. "RNA mediated gene expression regulation in Listeria." Paris 7, 2012. http://www.theses.fr/2012PA077233.

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Listeria monocytogenes est une bactérie pathogène responsable de la listériose, une maladie d'origine alimentaire. Alors que de nombreuses protéines de L. Monocytogenes ont été identifiées comme facteurs de virulence, le rôle des petits ARN régulateurs chez Listeria demeure méconnu. Mon projet de thèse avait pour objectif de découvrir de nouveaux concepts sur la régulation de l'expression des gènes impliquant des ARNs régulateurs jouant un rôle dans la virulence de Listeria. Mon travail a été basé sur deux approches distinctes. La première a concerné l'analyse comparative des transcriptomes de L. Monocytogenes et de L. Innocua, une espèce proche non-pathogène. La seconde a concerné la caractérisation de petits ARNs régulateurs et l'identification de leur rôle dans le processus infectieux. L'analyse comparative des deux transcriptomes a révélé une conservation de la majorité des transcrits, à l'exception d'une divergence significative entre les deux espèces pour un sous-ensemble d'ARN régulateurs non-codants. De manière surprenante, nous avons identifié une classe de longs transcrits antisens (lasARNs) qui chevauchent un gène tout en servant de S'UTR au gène adjacent divergent. La transcription du lasARN est à l'origine d'une régulation mutuellement exclusive de l'expression des gènes adjacents avec des fonctions opposées. Cette étude a été la première à comparer deux transcriptomes bactériens avec une résolution d'une seule base. Elle a conduit à la découverte chez L. Monocytogenes de 33 nouveaux petits ARNs et 53 asARNs et à l'identification d'une structure lasRNA /opéron que nous avons appelé « excludon» qui pourrait représenter une nouvelle forme de régulation chez les bactéries. J'ai également effectué une analyse sur plusieurs petits ARNs en combinant des approches de transcriptomes, des modèles d'infection chez la souris et en utilisant des algorithmes de prédiction de cibles des ARNs. J'ai ainsi identifié et caractérisé cinq petits ARNs qui sont importants pour la virulence de Listeria. Au cours de cette analyse, j'ai caractérisé en détail RliB, un ARN à double fonction pouvant agir comme un élément CRISPR et comme un ARN régulateur impliqué dans la régulation de l'homéostasie du fer chez Listeria. Nous avons ainsi réalisé la première étude détaillée d'un élément CRISPR impliqué dans la régulation d'un processus cellulaire fondamental autres que l'immunité contre les bactériophages
Listeria monocytogenes is a bacterial pathogen responsible for listeriosis, a food-borne disease. In contrast to the significant advances in identifying proteins involved in virulence, relatively little is known about the role of sRNAs in L. Monocytogenes pathogenesis. The aim of my thesis project was to discover new concepts in RNA-mediated gene expression regulation with a role in Listeria virulence. My work was based on two distinct approaches. The first one involved global transcriptomic studies of L. Monocytogenes and its non-pathogenic relative, Listeria innocua while the second one concerned the characterization of individual sRNAs and the identification of their role in the infectious process. First, our comparative transcriptome analysis revealed conservation across most transcripts, but significant divergence between the species in a subset of non-coding sRNAs. This study was the first to compare two bacterial transcriptomes at a single-base resolution. Pt led to the discovery of 33 new sRNAs and 53 new asRNAs in L. Monocytogenes. Remarkably, we identified a class of long antisense transcripts (lasRNAs) that overlap one gene while also serving as the 5'UTR of the adjacent divergent gene. IasRNA transcription leads to the mutually exclusive regulation of the adjacent genes with opposite functions. This IasRNA/operon structure that we named "excludon" might represent a novel form of regulation in bacteria. Second, we conducted an analysis on several sRNAs by combining transcriptomic approaches, target prediction algorithm and mouse model of infection. I thus identified and characterized five sRNAs that are important for Listeria virulence. Furthermore, I focused on the detailed characterization of RIiB, a dual-function regulatory RNA that acts as a CRISPR element and a regulatory RNA involved in Listeria iron homeostasis regulation, providing the first detailed study of CRISPR element regulating fundamental cellular processes other than acting as a bacteriophage defense system

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Smith, Gillian. "Xenobiotic regulation of cytochrome P450 gene expression." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/20797.

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Cytochromes P450 (P450) are a ubiquitous class of monooxygenases located in the endoplasmic reticulum of mammalian cells. These enzymes catalyse the Phase I oxidative metabolism of a wide range of structurally diverse chemicals resulting in increased hydrophilicity and excretion. Certain chemicals are, however, metabolically activated by cytochrome P450, leading to the formation of cytotoxic and/or carcinogenic metabolites. This has been exploited in the design of many prodrugs, including anti-tumour agents, which are inactive as administered but become active in vivo following metabolism by one or more of the P450 isozymes. The regulation of P450 gene expression has been well documented in experimental animals, but at present there is very little information available about the regulation of human P450 genes, particularly in extra-hepatic tissues. Regulation of P450 expression by a range of xenobiotics, known to have profound effects on the expression of rodent P450 genes, has been studied in a mouse model and in cultured cells. Of particular interest were the potent and pleiotropic effects on murine P450 expression of TCPOBOP (1,4 bis [s,(3,5-dichloropyridyloxy)] benzene), which showed marked tissue and species specificity in its inductive effects in rodents. A model was developed, using human tumours grown as xenografts in immune deficient mice, in which the in vivo regulation of human P450 genes could be examined. TCPOBOP was shown to be equally effective at influencing human P450 gene expression and, in most cases, the patterns of gene regulation observed in experimental animals were also seen in the human tumours. These studies suggest that modulation of intra-tumour P450 levels by agents such as TCPOBOP may lead to enhanced metabolism of anticancer drugs such as cyclophosphamide, which require P450-mediated activaion in order to exert their anti-tumour effects.

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Martins, Rute Isabel Paulo. "Post-transcriptional regulation of HFE gene expression." Doctoral thesis, FCT - UNL, 2010. http://hdl.handle.net/10362/5596.

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Thesis presented to obtain the Ph.D. degree in Biology (Molecular Genetics), by the Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia.
O ferro é um elemento essencial em diversos processos metabólicos celulares. O desafio que se coloca para a maioria dos organismos prende-se com o controlo do ferro absorvido de modo a suprir as necessidades destes processos evitando, no entanto, os danos causados pelo ferro livre. Na realidade, algumas das doenças humanas mais comuns estão relacionadas com a perturbação da homeostase do ferro. Entre estas, encontra-se a hemocromatose hereditária que, estando maioritariamente associada a mutações no gene HFE, origina a acumulação de ferro em vários órgãos. A proteína HFE actua na homeostase do ferro através da regulação da expressão da hepcidina no fígado. O principal transcrito HFE apresenta baixos níveis de expressão numa série de tecidos humanos, tendo sido descritos diversos transcritos adicionais. O trabalho aqui apresentado aborda a caracterização dos transcritos alternativos de HFE, os mecanismos envolvidos na sua génese, assim como o seu possível papel fisiológico e regulação. A análise de diversos tecidos humanos permitiu identificar vários transcritos HFE resultantes de splicing alternativo. O estudo funcional de algumas proteínas correspondentes demonstrou que o processo de splicing alternativo pode gerar variantes não funcionais ou produzir uma variante HFE solúvel que é secretada pelas células associada à beta2-microglobulina. Esta proteína poderá desempenhar um papel crucial na homeostase do ferro, actuando como um agonista ou antagonista da HFE full length. Além disso, foi demonstrado que a expressão do transcrito HFE principal é fisiologicamente regulada pelo mecanismo de nonsense-mediated mRNA decay (NMD), dado que os seus níveis aumentam quando este mecanismo é inibido. A pesquisa realizada em tecidos humanos permitiu verificar que a expressão do mRNA HFE resulta da utilização de quatro locais de clivagem e poliadenilação alternativos. Este padrão de poliadenilação alternativa específico de tecido aparenta responder a estímulos de ferro, actuando coordenadamente com o NMD no ajustamento dos níveis de expressão de HFE. Esta dissertação demonstra que a regulação da expressão do gene HFE é influenciada pós-transcricionalmente pelos mecanismos de splicing alternativo, poliadenilação alternativa e NMD. Este conhecimento poderá conduzir a novas perspectivas de investigação na área do metabolismo do ferro e contribuir para o delinear de novas estratégias terapêuticas a aplicar em patologias de homeostase do ferro através da regulação da hepcidina.

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47

Smith, Erin N. "Gene-environment interaction in yeast gene expression /." Thesis, Connect to this title online; UW restricted, 2008. http://hdl.handle.net/1773/5025.

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48

Samanta, Priyankar. "Gene Regulation in Biofilms." Thesis, North Dakota State University, 2011. https://hdl.handle.net/10365/29330.

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Sessile bacterial communities which form on the solid surface or solid-liquid interface are known as biofilms. Both single species and multispecies biofilms are characterized by an extracellular matrix of polymeric substances which gives them several hundred times more antibiotic resistances than a planktonic bacterial culture. Though bacteria are the most common causative agent of various diseases, because of the high antibiotic resistance, biofilms cause complications of various diseases like cystic fibrosis, prosthetic valve endocarditis, chronic pulmonary diseases, catheter-associated urinary tract infections and several other diseases. From past studies, quorum sensing has been established as a novel target mechanism against biofilms; in this study, the two-component signal transduction systems (2CSTSs) have been focused. Once better understood, 2CSTSs can serve as a novel drug target and prevention mechanism for biofilm associated diseases. According to prior high-throughput experiments and phenotype microarray experiments by our lab, several 2CSTSs like OmpR-EnvZ, RcsCDB along with the global regulator FlhD/FlhC were hypothesized to have an important effect on various developmental stages of biofilm formation. From that past study, we postulated that acetate metabolism may be an important aspect for biofilm formation. In this study, we tested and confirmed this hypothesis. We observed biofilms formed by several mutants in 2CSTS, as well as mutants in acetate metabolism, using Scanning Electron Microscopy (SEM). We found quantitative and qualitative differences in the biofilm of the acetate mutants when compared to their isogenic parental Escherichia coli strain. An additional mutation in rcsB with acetate mutant strains forms less clumpy biofilms whereas an additional mutation in dcuR results in the formation of less biofilms. So the structural and the quantitative differences of acetate mutant biofilms depend on additional mutations in rcsB and dcuR. Though a number of studies have been done on the temporal gene expression within biofilms, spatial gene expression of the mature biofilm is a big gap of knowledge. The future aim of this study is to study the temporal as well as the spatial gene expression of different 2CSTSs in the biofilm. In my MS thesis, I have constructed selected promoter fused GFP /RFP plasmids and some other fusion plasmids were purchased from the promoter collections from Open Biosystems, lastly E. coli AJW678 bacterial strains were transformed with these GFP /RFP fused plasmids. A 96 well microtiter plate assay was performed to study the temporal expression from the promoters by quantifying the fluorescence intensity in the planktonic culture. According to this experiment, the highest expression of flhD was after 20 hours whereas, the expression of ompR increases up to 7 days, which indicates that the flhD expresses earlier than ompR. The decreasing phase of flhD expression was paralleled by the sharpest increase in ompR expression as phosphorylated OmpR is an inhibitor of flhD expression.
National Institutes of Health (NIH grant 1R15AI089403)
United States. Animal and Plant Health Inspection Service

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Bradburne, James Andrew. "Regulation of nif gene expression in bradyrhizobium japonicum." Diss., Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/25742.

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50

Rouleau, Julie. "Regulation of the mouse DNA methyltransferase gene expression." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29122.

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A hallmark of DNA methylation is the fact that 60 to 80% of CpG dinucleotide sequences in the vertebrate genome are methylated at the 5th-position of cytosine while the remaining unmethylated sequences are nonrandomly distributed throughout the genome generating a pattern of methylation that is both tissue and gene specific. Several lines of evidence suggest that methylation patterns correlate with the expression level of eukaryotic genes and that DNA methylation plays an important role in regulating the state of differentiation of mammalian cells. The methylation of DNA is catalyzed by the DNA methyltransferase (DNA MeTase) enzyme, which transfers a methyl group from S-adenosylmethionine to DNA. Cells that exhibit different DNA methylation patterns express similar mRNA levels and DNA MeTase activities. It has therefore been suggested that patterns of methylations are the result of an interplay between the level of the nonspecific DNA MeTase enzyme and other site- or tissue-specific nuclear factors; changing either one of these parameters will result in a change in DNA methylation patterns. In accordance with this hypothesis it has been proposed that regulation of DNA methyltransferase gene expression plays a role in the maintenance and generation of DNA methylation patterns, as is the case in prokaryotic systems. Bestor et al., cloned the cDNA encoding the mouse DNA MeTase gene but nothing was known about the elements regulating its expression. To further understand regulation of the mouse DNA MeTase gene expression I cloned and sequenced the 5$ sp prime$-upstream region of the gene and demonstrated that: (A) The mouse DNA MeTase promoter is a unique housekeeping promoter lacking the classical binding sites for known transcription factors. (B) The mouse DNA MeTase is induced by the Ras-AP-1 pathway. (C) Induction of the mouse DNA MeTase by the Ras-AP-1 leads to profound changes in cell morphology, methylation patterns and tumorigenicity all of which can be inhib

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Dissertations / Theses on the topic 'Leukemic Gene Expression Regulation'

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