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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
451

Proteolytic cleavage of FOXM1 by caspases /

Deng, Meihong. January 2006 (has links)
Thesis (M. Med. Sc.)--University of Hong Kong, 2006.
452

The relationship between peroxisome proliferator-activated receptors (PPARs) and cell proliferation /

Cheng, Wai, January 2006 (has links)
Thesis (M. Med. Sc.)--University of Hong Kong, 2006.
453

Regulation of dsRNA-induced transcription by NFêB and IRF-3 through TLR3 and RIG-1

Elco, Christopher. January 2007 (has links)
Thesis (Ph. D.)--Case Western Reserve University, 2007. / [School of Medicine] Department of Molecular Virology. Includes bibliographical references. Available online via OhioLINK's ETD Center.
454

A role for p63 in the regulation of cell cycle progression and cell death

Helton, Eric Scott. January 2007 (has links) (PDF)
Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed June 30, 2007). Includes bibliographical references (p. 70-72).
455

Mss11p mediated regulation of transcription, pseudohyphal differentiation and flocculation in Saccharomyces cerevisiae

Franken, Jaco (Cornelius Jacobus) 03 1900 (has links)
Thesis (MSc)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: In all cellular systems the ability to alter eellular programs in response to extracellular cues is essential for survival. This involves the integration of signals triggered by membrane bound receptors in order to adjust the expression of target genes and enzyme activities and consequently phenotypic outcome. The yeast Saccharomyces cerevisiae has evolved several adaptations, such as, sporulation and pseudohyphal differentiation, in order to survive changes in the surrounding environment. Pseudohyphal differentiation and the related phenotype, invasive growth, are proposed to be adaptations that enable the yeast to forage for scarce nutrients or escape from a detrimental environment. This dimorphic transition is associated with a change from the normal "yeast" form to a pseudohyphal form, which involves changes in budding pattern, cell-cycle progression, cellular elongation, and cell-eell and cell-substrate adherence. The outcome of these changes is elongated eells, which bud in a unipolar fashion and do not separate after budding to form chains of cells referred to as pseudohyphae. These pseudohyphae are able to penetrate the surface of agar containing growth medium, a process referred to as invasive growth. Nutrient-induced adaptations, such as pseudohyphal growth, have been extensively studied in S. cere visiae , and several factors have been implicated in the regulation thereof, many of which are part of specific signalling pathways. The most clearly defined are the filamentous growth specific MAP kinase cascade and the Gpa2p-cAMP-PKA pathway. MUC1/FL011, encoding a member of a family of cell wall associated proteins involved in cellcell/ cell-substrate adhesion, is regulated by these pathways and considered to be critical in the establishment of pseudohyphal differentiation and invasive growth. The promoter region of MUC1/FL011 represents one of the largest yeast promoters identified to date, with cis-acting elements present up to 2.4 kb upstream from the first coding triplet. The upstream regulatory region of MUC1/FL011 is almost identical to that of the STA2 gene, which encodes an extracellular glucoamylase required for the utilisation of extracellular starch. As suggested by the extent of homology between these two promoters, MUC1/FL011 and STA2 are co-regulated to a large degree and both require the same transcription factors. Mss11p plays a central role in the regulation of MUC1/FL011 and STA2 and consequently starch metabolism and pseudohyphaI differentiation. The regulation conferred by MSS11 on the transcriptional levels of MUC1/FL011 and STA2 also appears to be dependent on signals generated specifically in the presence of low nitrogen and glucose. Mss11p does not have significant homology to any other yeast protein, with the exception of limited homology to the transcriptional activator F108p. However, several distinctive domains have been identified in the MSS11 gene product. Firstly, Mss11p contains polyglutamine and poly-asparagine domains. It also contains a putative ATP- or GTP-binding domain (P-Ioop), commonly found in proteins such as kinases, ATPases or GTPases. Two short stretches close to the N-terminal, labelled H1 and H2, share significant homology to the transcriptional activator, F108p. Both the H2 domain and the extreme C-terminal of Mss11p are able to stimulate RNA polymerase II dependent transcription. Furthermore, the H1 domain together with the P-Ioop negatively regulates the activation potential of the H2 domain. This study presents further insight into the functioning of Mss11p and the involvement of the separate activation and regulatory domains in mediating transcriptional activation and pseudohyphal differentiation in response to nutrient limitation. Genetic interactions between Mss11p and other factors involved in the regulation of pseudohyphal growth and starch degradation were revealed, and specific regions of Mss11p were shown to be required by these factors in order to achieve their required function. In addition, results obtained in this study implicates Mss11p in the regulation of Ca2+-dependent flocculation and suggest that the FL01 gene is also regulated by Mss11p in this capacity. / AFRIKAANSE OPSOMMING: Die vermoë om sellulêre programme in reaksie op ekstrasellulêre seine te verander, is 'n essensiële vereiste vir alle sellulêre sisteme. Dit behels die integrasie van seine gegenereer deur membraan-gebonde reseptore om ekspressie van teikengene en ensiemaktiwiteite sodanig aan te pas dat gewenste fenotipise uitkomste bewerkstellig kan word. Die gis Saccharomyces cerevisiae het verskeie aanpassingsmeganismes ontwikkel, soos byvoorbeeld sporulasie en pseudohifeforming, om veranderinge in die omgewing te kan oorleef. Pseudohifevorming en die verwante fenotipe, penetrasiegroei, word beskou as aanpassings te wees wat die gis in staat stel om van 'n skadelike omgewing weg te kom, of dit in staat te stelom by skaars voedingstowwe uit te kom. Hierdie dimorfiese transisie word geassosieer met 'n verandering van die normale "gisvorm" tot pseudohifevorming wat veranderinge in die botpatroon, selsiklusprogressie, selverlenging, sel-sel en sel-substraat aanhegting behels. Die uitkoms van hierdie verandering is verlengde selle, wat unipolêr bot en nie van mekaar skei nie om sodoende kettings van selle te vorm en waarna verwys word as pseudohifes. Hierdie pseudohifes is ook in staat om die oppervlak van 'n agar bevattende groeimedium te penetreer, 'n proses waarna verwys word as penetrasiegroei. Aanpassings soos pseudohitevorminq is die afgelope dekade intensief nagevors, en verskeie faktore en seintransduksienetwerke is in die regulering daarvan geïmpliseer. Onder hierdie seintransduksienetwerke is die bes gedefiniëerde paaie die filamentasie-spesifieke MAP-kinasekaskade en die Gpa2p-cAMP-PKA pad. MUC1/FL011 kodeer vir 'n lid van 'n geenfamilie wat met sel-sel/sel-substraat aanhegting geasosieer word en dit word deur hierdie seintransduksie netwerke gereguleer. MUC1/FL011 word as essensieel vir pseudohife vorming beskou. MUC1/FL011 word gereguleer deur die grootste gispromoter wat tot op hede geïdentifiseer is, met cis-werkende elemente so ver as 2.4 kb stroom-op van ATG. Die MUC1/FL011 promoter is feitlik identies tot die van die STA2-geen, wat kodeer vir 'n ekstrasellulêre glukoamilase wat die gis in staat stelom ekstrasellulêre stysel te benut. Weens die homologie tussen die twee promoters, word MUC1/FL011 en STA2 tot In groot mate ge-koreguleer en beide benodig dieselfde transkripsiefaktore. Mss11p speel In sentrale rol in die regulering van MUC1/FL011 en STA2 en dus ook in die regulering van pseudohifevorming en styselmetabolisme. Die regulering wat deur Mss11p of MUC1/FL011 en STA2 uitgeofen word, blyk verder onderhewig te wees aan seine wat gegenereer word spesifiek in die teenwoordigheid van lae konsentrasies glukose en stikstof. Mss11p het nie betekenisvolle homologie met enige ander gisproteïen nie, behalwe vir beperkte homologie met die tranksripsionele aktiveerder F108p. Verskeie onderskeidbare domeine is egter in die MSS11 geenproduk teenwoordig. Eerstens, Mss11p bevat kenmerkende poliglutamien en poli-asparagien domeine. Verder bevat Mss11p ook In voorspelde ATP- of GTP-bindings domein (P-Ius), wat algemeen in proteïene soos kinases, ATPasaes en GTPases voorkom. Twee kort areas naby die N-terminaal, aangedui as H1 en H2, het betekenisvolle homologie met die transkripsiefaktor F108p. Beide die H2 domein en die ektreme C-terminaal van Mss11p is in staat om RNA polimerase " afhanklike transkripsie te stimuleer. Verder het die H1-domein in samewerking met die P-Ius In negatiewe uitwerking op die aktiveringspotensiaal van die H2-domein. Hierdie studie bied verdere insig tot die werking van Mss11p en die betrokkenheid van die verskeie aktiverings- en reguleringsdomeine by die oemiddetlinq van transkripsionele aktivering en pseudohifevorming in reaksie op beperking van voedingstowwe. Genetiese interaksies tussen Mss11p en ander faktore betrokke met die regulering van pseudohifevorming en styselafbraak is in hierdie studie aangetoon. Voorts is daar ook gewys dat spesifieke areas van Mss11p benodig word deur hierdie faktore om hulle biologiese funksie uit te oefen. Daar is ook In rol vir Mss11p in die regulering van Ca2+-afhanklike flokkulasie aangetoon en daar is bewys dat die FL01 geen deur Mss11p benodig word om hierdie effek uit te oefen.
456

Analysis of cyclin H interaction with non-coding RNAs

O'Gorman, William Evert January 2007 (has links)
No description available.
457

Characterising the determinants of hypoxia inducible transcription factors binding to chromatin

Smythies, James January 2017 (has links)
Hypoxia regulates many hundreds of genes that play important roles in numerous physiological and pathophysiological processes. The hypoxia inducible transcription factors (HIFs) are central to the transcriptional activation of these hypoxia-regulated genes. However, to date, little is known about the determinants of HIF-1 and HIF-2 binding site selection. Both HIF-1 and HIF-2 appear to bind as HIF-α/HIF-1β heterodimers, and recognise the same core consensus DNA motif, the hypoxia response element (HRE). However, each has its own distinct but partially overlapping set of binding sites that accounts for only a subset of the total accessible HRE motifs. Here, I have utilised ChIP-seq to systematically compare pan-genomic HIF-1α, HIF-2α and HIF-1β DNA binding in multiple cell lines and have related this to RNA-seq analyses and other publically-accessible next-generation sequencing datasets. I show that endogenous HIF-Iα subunits exhibit a high-degree of binding site concordance with HIF-1β, consistent with largely canonical binding of intact heterodimers. Despite cell-type specific differences in HIF-1 and HIF-2 binding site occupancy, each isoform exhibits a remarkable rigidity in its preference to bind either promoter-proximal or promoter-distal sites, respectively. These specific distribution patterns are unaffected by the absence of the other HIF-Iα subunit, suggesting that they do not result from exclusion of one isoform by competition with the other, but rather are discrete properties of each. Furthermore, hypoxia regulated genes neighbouring sites that are shared by both HIF-1 and HIF-2 are more likely to be regulated by HIF-1 when the site is closer to the gene and by HIF-2 when further away, indicating that post-binding mechanisms of transcriptional regulation also follow a similar pattern. Comparison of sites preferentially bound by HIF-1 and HIF-2, respectively, revealed associations with distinct histone environments, distinct accessory transcription factor binding motifs and distinct patterns of transcription factor binding site occupancy, suggesting that each may be influencing specific HIF-1 and HIF-2 binding site selection. In particular, both the AP-1 motif and AP-1 binding site occupancy were enriched within HIF-2 binding sites compared to HIF-1 sites. Intervention on AP-1 DNA-binding using the dominant-negative protein, AFos, attenuated HIF binding, specifically at sites co-occupied by AP-1 and HIF. This indicates that a cooperative relationship exists between the two transcription factors. However, binding of both HIF-1α and HIF-2α were affected suggesting that while AP-1 binding may account for the ability of HIF to bind some HRE motifs but not others, it is not a determinant of differential binding between the two isoforms. Overall, this work reveals remarkably distinct and functionally relevant patterns of HIF-1 and HIF-2 binding across the genome, and provides insight into underlying mechanisms of binding.
458

Investigation of transcriptional regulation of Foxn1 in fetal thymic epithelial progenitor cells

Vaidya, Harsh Jayeshkumar January 2016 (has links)
The thymus in mice and humans originates from the third pharyngeal pouch endoderm. This process is divided into early Foxn1-independent stages and later Foxn1-dependent stages. Foxn1 is indispensible for the differentiation of thymic epithelial progenitor cells (TEPCs) as the development of thymus in Foxn1 mutant mice is arrested around E12.5. The transcriptional changes associated with the developmental of the thymus are poorly understood. In particular, the transcriptional regulation of Foxn1 in the developing thymic rudiment has not been definitively identified. Recently, Pax1, Pax9, Tbx1, and E2Fs have been implicated in transcriptional regulation of Foxn1. However, with the exception of E2Fs, evidence regarding their direct involvement in regulating Foxn1 expression is missing. Therefore, the aims of this thesis were to study the transcriptional regulation of Foxn1 through identification of its regulatory regions and studying the transcriptional changes associated with the developing thymus. These aims were addressed through the use of chromatin-immunoprecipitation technique combined with next-generation sequencing and gene expression analyses of the developing TEPCs. The data presented in this thesis identified H3K4me3 and H3K27ac marked Foxn1 promoter and five H3K4me1 and H3K27ac marked putative enhancer regions. The combination of gene expression analyses and transcription factor binding sites within the above regions suggested Ets1, Isl1, Foxc1, Nfia, Nfib, Srf, Foxo1, Nfatc2, Ing4, Foxa2, Hes1, E2Fs, and p53 as candidate transcriptional regulators of Foxn1. Nfatc2 appears also to be a target of Foxn1 that could play an important role in thymus development by regulating a large set of genes. Comparison of wild type and Foxn1 null thymus showed that Foxn1 could act as positive regulator of Pax1 and negative regulator of Gata3 and Eya1, genes important for third pharyngeal pouch development. The comparison of transcriptome of E10.5 and E11.5 third pharyngeal pouch cells and E12.5 TEPCs showed that genes involved in tissue development are downregulated while those involved in antigen presentation, a process important for thymus function, are upregulated during development. These results also demonstrated a decrease in the activity of transcription factor network involving Hox genes and an increase in the activity of a network involving Nfkb, Rela, and Irf genes. Analysis of signalling pathways suggested that the NFκB signalling pathway could be important for thymus development after E12.5 while TGFβ signalling pathway appeared to be detrimental to Foxn1 expression in thymic epithelial cells. Together, I identified several transcription factors that could be involved in transcriptional regulation of Foxn1 in TEPCs, several genes that could be a target of FOXN1, changes in transcription factor network and signalling pathways associated with the developing thymic rudiment.
459

The role of DNA methylation on transcription factor occupancy and transcriptional activity

Cusack, Martin January 2017 (has links)
DNA methylation is an epigenetic mark that is deposited throughout the genome of mammals and plays an important role in the maintenance of transcriptionally repressive states across cell divisions. There are two major mechanisms by which DNA methylation has been proposed to act: one involves the recognition of the mark by protein complexes containing histone deacetylases (HDACs) that can remodel the local chromatin. Alternatively, methylation has been suggested to directly affect the interaction between transcription factors and their cognate binding sequence. The aim of this research was to determine the contributions of these two mechanisms in cells. The importance of HDAC activity in mediating DNA methylation-dependent transcriptional repression was assessed by comparing the genes and retrotransposons that are upregulated in response to DNA methylation loss or the disruption of HDAC activity. To this purpose, we performed whole-genome transcriptional analysis in wild type and DNA methylation-deficient mouse embryonic stem cells (DNMT.TKO mESCs) in the presence and absence of the HDAC inhibitor trichostatin A. Our data suggests that there are few genes whose repression is solely dependent on the recruitment of HDACs by DNA methylation in mESCs. Rather it appears that DNA methylation and HDAC-mediated silencing represent two independent layers of repression that converge at certain transcriptional elements. To investigate the contribution of DNA methylation on the genome-wide occupancy of transcription factors, we compared the global chromatin accessibility landscape and the binding profile of candidate transcription factors in the absence or presence of DNA methylation. We found that loss of DNA methylation associates with localised gains in accessibility, some of which can be linked to the novel binding of transcription factors such as GABPA, MAX, NRF1 and YY1. Altogether, our results present new insights into the interplay between DNA methylation and histone deacetylation and their impact on the localisation of transcription factors from different families.
460

Acido graxo aumenta a secreção de insulina e modula a expressão de genes envolvidos na biossintese de insulina em ilhotas de ratos submetidos a desnutrição proteica / Free fatty acids increase insulin secretion and modulates expression of genes involved in insulin biosynthesis in islets from malnourished rats

Arantes, Vanessa Cristina 27 March 2006 (has links)
Orientador: Antonio Carlos Boschero / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-06T07:06:58Z (GMT). No. of bitstreams: 1 Arantes_VanessaCristina_D.pdf: 1696436 bytes, checksum: 2db258b560bf7ee0ec64de7441adfe76 (MD5) Previous issue date: 2006 / Resumo: Em animais, a desnutrição intra-uterina exerce efeitos marcantes sobre o desenvolvimento fetal e pós-natal. Sabe-se que animais desnutridos apresentam níveis elevados de ácidos graxos plasmáticos e esses, por sua vez, são responsáveis por alterar a secreção de insulina. Neste trabalho, verificamos a expressão do fator de transcrição PDX-1, da p38/SAPK2, o metabolismo da glicose e a secreção de insulina em ilhotas de ratos mantidos durante o período fetal e da lactação com uma dieta normoprotéica (17% de proteína) ou hipoprotéica (6% de proteína). Cultivamos as ilhotas por 48 horas em meio de cultura contendo 5.6 mM/L de glicose, na ausência ou presença de0.6 mM/L de ácido palmítico. A secreção de insulina em ilhotas isoladas em resposta 16,7 mmol/L de glicose foi reduzida em ratos desnutridos, no entanto, quando na presença de ácido graxo, observou-se um aumento. Em 2.8 mmol glicose/L,houve diminuição do metabolismo da glicose em ilhotas de desnutridos .Entretanto, quando estimuladas com 16.7 mmol/L de glicose, tanto as ilhotas de desnutridos como as do controle, apresentaram acentuada redução na oxidação da glicose, na presença de ácido graxo. Os níveis de mRNA do PDX-1 e da insulina aumentaram significativamente quando na presença de ácido graxo em ambos os grupos. O efeito do ácido palmítico sobre a expressão protéica de PDX-1 e da p38/SAPK2 apresentou-se similar em ambos os grupos, mas o aumento foi muito mais evidente em ilhotas de desnutridos. Esses resultados demonstram a complexa relação entre nutrientes no controle da secreção de insulina e mostram queos ácidos graxos desempenham um papel importante na homeostasia da glicose, por afetar mecanismos moleculares e as vias de acoplamentsecreção de insulina / Abstract: A severe reduction in insulin release in response to glucose is consistently noticed in protein-deprived rats and is attributed partly to the chronic exposure to elevated levels of free fatty acids. Since the pancreatic and duodenal transcription factor homeobox 1 (PDX-1) is important for the maintenance of B-cell physiology, and since PDX-1 expression is altered in the islets of rats fed a low protein diet, we assessed PDX-1 and insulin mRNA expression, as well as PDX-1 and p38/SAPK2 protein expression, in islets from young rats fed low (6%; LP) or normal (17%; C) protein diets and maintained for 48 h in culture medium containing 5.6 mmol glucose/L with or without 0.6 mmol palmitic acid/L. We also measured glucoseinduced insulin secretion and glucose metabolism. Insulin secretion by isolated islets in response to 16.7 mmol glucose/L was reduced in LP compared to C rats. In the presence of free fatty acids, there was an increase in insulin secretion in both groups At 2.8 mmol glucose/L, the metabolism of this sugar was reduced in LP islets, regardless of the presence of this fatty acid. However, when challenged with 16.7 mmol glucose/L, LP and C islets showed a severe reduction in glucose oxidation in the presence of free fatty acid. The PDX-1 and insulin mRNA were significantly higher when free fatty acid was added to the culture medium in both groups of islets.The effect of palmitic acid on PDX-1 and p38/SAPK2 protein levels was similar in LP and C islets, but the increase was much more evident in LP islets. These results demonstrate the complex interrelationship between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis by affecting molecular mechanisms and stimulus/secretion coupling pathways / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular

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