Дисертації з теми "Eukaryotic gene regulation"
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Kielbasa, Szymon M. "Bioinformatics of eukaryotic gene regulation." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=982693192.
Повний текст джерелаKiełbasa, Szymon M. "Bioinformatics of eukaryotic gene regulation." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2006. http://dx.doi.org/10.18452/15562.
Повний текст джерелаUnderstanding the mechanisms which control gene expression is one of the fundamental problems of molecular biology. Detailed experimental studies of regulation are laborious due to the complex and combinatorial nature of interactions among involved molecules. Therefore, computational techniques are used to suggest candidate mechanisms for further investigation. This thesis presents three methods improving the predictions of regulation of gene transcription. The first approach finds binding sites recognized by a transcription factor based on statistical over-representation of short motifs in a set of promoter sequences. A succesful application of this method to several gene families of yeast is shown. More advanced techniques are needed for the analysis of gene regulation in higher eukaryotes. Hundreds of profiles recognized by transcription factors are provided by libraries. Dependencies between them result in multiple predictions of the same binding sites which need later to be filtered out. The second method presented here offers a way to reduce the number of profiles by identifying similarities between them. Still, the complex nature of interaction between transcription factors makes reliable predictions of binding sites difficult. Exploiting independent sources of information reduces the false predictions rate. The third method proposes a novel approach associating gene annotations with regulation of multiple transcription factors and binding sites recognized by them. The utility of the method is demonstrated on several well-known sets of transcription factors. RNA interference provides a way of efficient down-regulation of gene expression. Difficulties in predicting efficient siRNA sequences motivated the development of a library containing siRNA sequences and related experimental details described in the literature. This library, presented in the last chapter, is publicly available at http://www.human-sirna-database.net
Webb, Sarah. "Structural analysis of eukaryotic gene regulation." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/13487.
Повний текст джерелаDickinson, P. "Fibronectin gene expression in higher eukaryotic cells." Thesis, University of Manchester, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378322.
Повний текст джерелаSpies, 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.
Повний текст джерелаThis 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.
Sen, Rwik. "REGULATION OF EUKARYOTIC TRANSCRIPTIONAL ELONGATION AND ASSOCIATED DNA REPAIR." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/dissertations/1205.
Повний текст джерелаHelder, Stephanie. "Investigations into RNA-binding proteins involved in eukaryotic gene regulation." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/18597.
Повний текст джерелаTo, Tsz-Leung. "Transcriptional bursting in eukaryotic gene regulation : molecular basis and functional consequences." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/62062.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references.
Transcription of mRNA appears to occur in random, intermittent bursts in a large variety of organisms. The statistics of mRNA expression can be described by two parameters: the frequency at which bursts occur (burst frequency) and the average number of mRNA produced within each burst (burst size). The mean steady-state abundance of mRNA is the product of the burst size and burst frequency. Although the experimental evidence for bursty gene transcription is abundant, little is known about its origins and consequences. We utilize single-molecule mRNA imaging and simple stochastic kinetic models to probe and understand both the mechanistic details and functional responses of transcriptional bursting in budding yeast. At the molecular level, we show that gene-specific activators can control both burst size and burst frequency by differentially utilizing kinetically distinct promoter elements. We also recognize the importance of activator residence time and nucleosome positioning on bursting. This investigation exemplifies how we can exploit spontaneous fluctuations in gene expression to uncover the molecular mechanisms and kinetic pathways of transcriptional regulation. At the network level, we demonstrate the important phenotypic consequences of transcriptional bursting by showing how noise itself can generate a bimodal, all-or-none gene expression profile that switches spontaneously between the low and high expression states in a transcriptional positive-feedback loop. Such bimodality is a hallmark in decision-making circuitry within metabolic, developmental, and synthetic gene regulatory networks. Importantly, we prove that the bimodal responses observed in our system are not due to deterministic bistability, which is an often-stated necessary condition for allor- none responses in positive-feedback loops. By clarifying a common misconception, this investigation provides unique biological insights into the molecular components, pathways and mechanisms controlling a measured phenotype.
by Tsz-Leung To.
Ph.D.
Ferdoush, Jannatul. "Regulation of nuclear phase of eukaryotic gene expression by ubiquitin-proteasome system." OpenSIUC, 2019. https://opensiuc.lib.siu.edu/dissertations/1751.
Повний текст джерелаZheng, Qun. "Analysis of the Caenorhabditis elegans rpc-1 gene." Diss., Columbia, Mo. : University of Missouri-Columbia, 2005. http://hdl.handle.net/10355/4129.
Повний текст джерелаThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (January 25, 2007) Vita. Includes bibliographical references.
Lahudkar, Shweta L. "REGULATION OF EUKARYOTIC GENE EXPRESSION BY mRNA CAP BINDING COMPLEX AND CAPPING MACHINERY." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/dissertations/834.
Повний текст джерелаWaters, Lorna Catherine. "Solution structures of proteins and complexes involved in the regulation of eukaryotic gene expression." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/29722.
Повний текст джерелаTsai, Pei-Fang. "TAF1 regulation of gene expression genome-wide localization and transcription profiling /." Diss., [Riverside, Calif.] : University of California, Riverside, 2010. http://proquest.umi.com/pqdweb?index=0&did=2019822761&SrchMode=2&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1273863805&clientId=48051.
Повний текст джерелаIncludes abstract. Available via ProQuest Digital Dissertations. Title from first page of PDF file (viewed April 24, 2010). Includes bibliographical references. Also issued in print.
Boland, Andreas [Verfasser], and Thilo [Akademischer Betreuer] Stehle. "Structural characterization of eukaryotic mRNA decay factors involved in post-transcriptional gene regulation / Andreas Boland ; Betreuer: Thilo Stehle." Tübingen : Universitätsbibliothek Tübingen, 2014. http://d-nb.info/1163235474/34.
Повний текст джерелаParkin, Neil T. "Regulation of gene expression by the 5' untranslated region of eukaryotic mRNAS : c-myc and HIV-1 as examples." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74327.
Повний текст джерелаLarsson, Ola. "Transcriptome studies of cell-fate and aging /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-296-9/.
Повний текст джерелаLee, Yun-Young. "Translational regulation of growth arrest and DNA damage-inducible gene GADD34 via its 5' untranslated region upstream open reading frame during eukaryotic initiation factor 2 alpha phosphorylation." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/17442.
Повний текст джерелаRapone, Roberta. "Essential cytoplasmic role(s) of the histone lysine methyltransferase Setdb1 in post-transcriptional regulation of gene expression." Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/RAPONE_Roberta_va.pdf.
Повний текст джерелаSetdb1 is a “histone” lysine methyltransferase (KMT) belonging to the SUV39 family that methylates lysine 9 of histone H3 (H3K9), one of the major epigenetic machineries mainly involved in gene repression. Notably, Setdb1 establishes mono-, di- and tri-methylation of H3K9. Setdb1, or Eset in mice, is essential for the survival, the pluripotency and the self-renewal of mouse embryonic stem cells (mESCs); Eset knockout is lethal at the peri-implantation stage at 3.5 dpc in mice. Setdb1 is also required for the differentiation of many progenitor cell types: spermatogenesis, neurogenesis, chondrocyte differentiation and skeletal muscle differentiation. Moreover, Setdb1 has been associated with several diseases: it is amplified in melanoma and lung cancer and it is dysregulated in liver, prostate, colorectal and breast cancers, Huntington disease and schizophrenia.Remarkably, beyond histones, Setdb1 methylates many non-histone substrates, such as UBF, p53, AKT, Tat and ING2 proteins. Although Setdb1 has been always associated with its nuclear role, it turns out that Setdb1 is the only H3K9 KMT to have also a cytoplasmic localization, in several cell types, including mESCs, mouse embryonic fibroblasts (MEFs) and HeLa cells. However, the function of Setdb1 in the cytoplasm remains totally unknown. To investigate Setdb1 cytoplasmic role, we have used mouse embryonic stem cells (mESCs), in which Setdb1 is essential. Our results show that cytoplasmic Setdb1 is crucial for the survival of mESCs: indeed, the number of apoptotic cells increases after the loss of cytoplasmic Setdb1. We found that cytoplasmic Setdb1 affects newly protein synthesis in mESCs. We further show that cytoplasmic Setdb1 interacts with mESCs-specific protein Trim71 (also called Lin41) and with the initiation translation factor eIF3c in mESCs. Finally, we reported that Setdb1 and Trim71 together co-regulate mRNA stability and translation. Our current data unravel the essential cytoplasmic function of Setdb1, for long time considered exclusively an “histone” lysine methyltransferase, and provide new insights into the post-transcriptional regulation of gene expression mediated by a fundamental epigenetic regulator
Pereira, Dirce Maria Carraro. "Regulação transcricional por glicose do promotor do gene que codifica celobiohidrolase I de Trichoderma reesei em Saccharomyces cerevisiae." Universidade de São Paulo, 1998. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-27112014-152253/.
Повний текст джерелаThe cellulotic system of the filamentous fungus Trichoderma reesei is transcriptionally induced 1000 -fold in presence of cellulose and is strongly repressed by glucose. Using the promoter deletion approach, the upstream activating region (UARcbl) responsible for cellulose-stimulated transcription of the major member of the cellulase system, cellobiohydrolase I, was localized between -241 and -72 relative to the TATA box. In this work we show that this region controls transcription and mediates glucose repression of a reporter gene in Saccharomyces cerevisiae, a unicellular microorganism that lacks the genes required for the utilization of cellulose. Glucose-controlled transcription mediated by the UARcbl requires the product of SNF1 gene, a protein kinase, and two repressors SSN6 and TUP1, which are well estalished in controlling glucose-represible yeast genes. Our results indicate a conserved mechanism of glucose control in eukariotic microorganisms.
Junetha, Syed Jabarulla. "Chemical Biology Approaches for Regulating Eukaryotic Gene Expression." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/202664.
Повний текст джерелаBonaccorsi, Eric D\'Alessandro. "Regulação da expressão gênica por oxigênio em microrganismos eucariotos: análises de ESTs (Expressed Sequence Tags) e microrrays de cDNA de Trichoderma reesei." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-04052018-110230/.
Повний текст джерелаGlucose and oxygen are essential molecules in most of living organisms. In addition to their importance in production of energy - glucose as a carbon and energy source and oxygen as an acceptor of electrons donated by NADH and FADH2 - both molecules function as effectors modulating various metabolic and physiological processes in the cell. Because one of the targets affected by both molecules is the mitochondrion, we isolated and sequenced the mitochondrial genome of Trichoderma reesei, a multicellular fungus that is used in this study as a model system. The effect of varying the concentration of glucose and oxygen on the expression of the transcripts of the mitochondrial genome, and its implication on the metabolism of glucose, was studied. Gene-wide expression analyses of nearly 2000 transcripts of T. reesei under limited concentration of dissolved oxygen, using cDNA microarry technique, are presented. At least 330 transcripts were differentially expressed with respect to oxygen availability. Those involved in protein synthesis and cell division processes were downregulated, while transcripts involved in cell defense and RNA synthesis were upregulated. A substantive fraction of other anaerobically affected genes have currently unknown cellular roles, and these results should therefore contribute to further functional annotation of the genome. ln addition, we have identified transcriptional regulators that are differentially expressed at a low oxygen tensions. The expression profile of these regulators points them out as potential candidates involved in the expression of genes affected by oxygen availability.
Kobir, Ahasanul. "Physiological roles of Eukaryotic Hanks type Ser/Thr kinase in transition to stationary phase in Bacillus subtilis." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00911812.
Повний текст джерелаKielbasa, Szymon M. [Verfasser]. "Bioinformatics of eukaryotic gene regulation / von Szymon M. Kielbasa." 2006. http://d-nb.info/982693192/34.
Повний текст джерелаVockley, Christopher Vockley. "Quantifying Eukaryotic Gene Regulation in Hormone Response and Disease." Diss., 2016. http://hdl.handle.net/10161/12886.
Повний текст джерелаQuantifying the function of mammalian enhancers at the genome or population scale has been longstanding challenge in the field of gene regulation. Studies of individual enhancers have provided anecdotal evidence on which many foundational assumptions in the field are based. Genome-scale studies have revealed that the number of sites bound by a given transcription factor far outnumber the genes that the factor regulates. In this dissertation we describe a new method, chromatin immune-enriched reporter assays (ChIP-reporters), and use that approach to comprehensively test the enhancer activity of genomic loci bound by the glucocorticoid receptor (GR). Integrative genomics analyses of our ChIP-reporter data revealed an unexpected mechanism of glucocorticoid (GC)-induced gene regulation. In that mechanism, only the minority of GR bound sites acts as GC-inducible enhancers. Many non-GC-inducible GR binding sites interact with GC-induced sites via chromatin looping. These interactions can increase the activity of GC-induced enhancers. Finally, we describe a method that enables the detection and characterization of the functional effects of non-coding genetic variation on enhancer activity at the population scale. Taken together, these studies yield both mechanistic and genetic evidence that provides context that informs the understanding of the effects of multiple enhancer variants on gene expression.
Dissertation
D'Espaux, Leopold Daniel. "Synthetic Regulation of Eukaryotic Gene Expression by Noncoding RNA." Thesis, 2013. https://thesis.library.caltech.edu/7852/13/dEspaux_2013_Thesis_Full.pdf.
Повний текст джерелаSynthetic biological systems promise to combine the spectacular diversity of biological functionality with engineering principles to design new life to address many pressing needs. As these engineered systems advance in sophistication, there is ever-greater need for customizable, situation-specific expression of desired genes. However, existing gene control platforms are generally not modular, or do not display performance requirements required for robust phenotypic responses to input signals. This work expands the capabilities of eukaryotic gene control in two important directions.
For development of greater modularity, we extend the use of synthetic self-cleaving ribozyme switches to detect changes in input protein levels and convey that information into programmed gene expression in eukaryotic cells. We demonstrate both up- and down-regulation of levels of an output transgene by more than 4-fold in response to rising input protein levels, with maximal output gene expression approaching the highest levels observed in yeast. In vitro experiments demonstrate protein-dependent ribozyme activity modulation. We further demonstrate the platform in mammalian cells. Our switch devices do not depend on special input protein activity, and can be tailored to respond to any input protein to which a suitable RNA aptamer can be developed. This platform can potentially be employed to regulate the expression of any transgene or any endogenous gene by 3’ UTR replacement, allowing for more complex cell state-specific reprogramming.
We also address an important concern with ribozyme switches, and riboswitch performance in general, their dynamic range. While riboswitches have generally allowed for versatile and modular regulation, so far their dynamic ranges of output gene modulation have been modest, generally at most 10-fold. We address this shortcoming by developing a modular genetic amplifier for near-digital control of eukaryotic gene expression. We combine ribozyme switch-mediated regulation of a synthetic TF with TF-mediated regulation of an output gene. The amplifier platform allows for as much as 20-fold regulation of output gene expression in response to input signal, with maximal expression approaching the highest levels observed in yeast, yet being tunable to intermediate and lower expression levels. EC50 values are more than 4 times lower than in previously best-performing non-amplifier ribozyme switches. The system design retains the modular-input architecture of the ribozyme switch platform, and the near-digital dynamic ranges of TF-based gene control.
Together, these developments suggest great potential for the wide applicability of these platforms for better-performing eukaryotic gene regulation, and more sophisticated, customizable reprogramming of cellular activity.
Wood, Lawrence Kent. "Mechanisms of Eukaryotic Copper Homeostasis." Diss., 2010. http://hdl.handle.net/10161/3122.
Повний текст джерелаCopper (Cu) is a co-factor that is essential for oxidative phosphorylation, protection from oxidative stress, angiogenesis, signaling, iron acquisition, peptide hormone maturation, and a number of other cellular processes. However, excess copper can lead to membrane damage, protein oxidation, and DNA cleavage. To balance the need for copper with the necessity to prevent accumulation to toxic levels, cells have evolved sophisticated mechanisms to regulate copper acquisition, distribution, and storage. The basic components of these regulatory systems are remarkably conserved in most eukaryotes, and this has allowed the use of a variety of model organisms to further our understanding of how Cu is taken into the cell and utilized.
While the components involved in Cu uptake, distribution, and storage are similar in many eukaryotes, evolution has led to differences in how these processes are regulated. For instance, fungi regulate the components involved in Cu uptake and detoxification primarily at the level of transcription while mammals employ a host of post-translational homeostatic mechanisms. In
Higher eukaryotes including mice and humans regulate Cu uptake predominately by means of post-translational control of the localization and stability of the Cu transport proteins. One of these proteins, Ctr1, is the primary means of Cu uptake into the cell, and members of the highly conserved Ctr family of Cu ion channels have been shown to mediate high affinity Cu(I) uptake into cells. In yeast and cultured human cells, Ctr1 functions as a homo-trimer with each monomer harboring an amino-terminal extracellular domain, three membrane spanning domains, a cytoplasmic loop, and a cytoplasmic tail. In addition to the highly conserved Ctr1 Cu ion importer, the baker's yeast
In mice and humans a gene encoding a protein with significant similarity to the
Dissertation
Sogo, Steven G. "Studies of novel methods of gene transfer and gene regulation in eukaryotic cells." Thesis, 1989. https://thesis.library.caltech.edu/5632/1/Sogo_sg_1989.pdf.
Повний текст джерелаShetty, Ameet S. "Regulation of the Saccharomyces cerevisiae INO1 gene: Novel insights into a hallmark of eukaryotic transcription regulation." 2011. https://scholarworks.umass.edu/dissertations/AAI3482726.
Повний текст джерелаSchmitz, Robert J. "Vernalization : a model for investigating epigenetics and eukaryotic gene regulation in Arabidopsis thaliana /." 2007. http://www.library.wisc.edu/databases/connect/dissertations.html.
Повний текст джерелаBasu, Deblina. "Identification and Characterisation of a miRNA releasing activity from Caenorhabditis elegans." Thesis, 2019. https://etd.iisc.ac.in/handle/2005/4366.
Повний текст джерелаUGC
Young, Sara Kathryn. "Upstream open reading frames differentially regulate genespecific translation in the integrated stress response." Diss., 2016. http://hdl.handle.net/1805/10606.
Повний текст джерелаGene expression is a highly coordinated process that relies upon appropriate regulation of translation for protein homeostasis. Regulation of protein synthesis largely occurs at the initiation step in which the translational start site is selected by ribosomes and associated initiating factors. In addition to the coding sequences (CDS) for protein products, short upstream open reading frames (uORFs) located in the 5’-leader of mRNAs are selected for translation initiation. While uORFs are largely considered to be inhibitory to translation at the downstream CDS, uORFs can also promote initiation of CDS translation in response to environmental stresses. Multiple transcripts associated with stress adaptation are preferentially translated through uORF-mediated mechanisms during activation of the Integrated Stress Response (ISR). In the ISR, phosphorylation of α subunit of the translation initiation factor eIF2α (eIF2α~P) during environmental stresses results in a global reduction in protein synthesis that functions to conserve energy and nutrient resources and facilitate reprogramming of gene expression. Many key regulators of the ISR network are subject to preferential translation in the response to eIF2α-P. These preferentially translated genes include the pro-apoptotic transcriptional activator Chop that modifies gene expression programs, feedback regulator Gadd34 that targets the catalytic subunit of protein phosphatase 1 to dephosphorylate eIF2α~P, and glutamyl-prolyl tRNA synthetase Eprs that increases the charged tRNA pool and primes the cell for resumption of protein synthesis after stress remediation. Ribosome bypass of at least one inhibitory uORF is a common theme between Chop, Gadd34, and Eprs, which allows for their regulated expression in response to cellular stress. However, different features encoded within the uORFs of the Chop, Gadd34, and Eprs mRNAs provide for regulation of their inhibitory functions, illustrating the complexities of uORF-mediated regulation of gene-specific translation. Importantly, preferentially translated ISR targets can also be transcriptionally regulated in response to cellular stress and misregulation of transcriptional or translational expression of Gadd34 can elicit maladaptive cell responses that contribute to disease. These mechanisms of translation control are conserved throughout species, emphasizing the importance of translation control in appropriate gene expression and the maintenance of protein homeostasis and health in diverse cellular conditions.
Joseph, Asha Mary. "Exploring the Evolution of Cellobiose Utilization in Shigella Sonnei And the Conservation of ChbG Orthologs in Eukaryotes." Thesis, 2016. http://etd.iisc.ac.in/handle/2005/2710.
Повний текст джерелаJoseph, Asha Mary. "Exploring the Evolution of Cellobiose Utilization in Shigella Sonnei And the Conservation of ChbG Orthologs in Eukaryotes." Thesis, 2016. http://etd.iisc.ernet.in/handle/2005/2710.
Повний текст джерелаDey, Souvik. "Transcriptional regulation of ATF4 is critical for controlling the Integrated Stress Response during eIF2 phosphorylation." Thesis, 2012. http://hdl.handle.net/1805/3041.
Повний текст джерелаIn response to different environmental stresses, phosphorylation of eIF2 (eIF2P) represses global translation coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of the integrated stress response, a program of gene expression involved in metabolism, nutrient uptake, anti-oxidation, and the activation of additional transcription factors, such as CHOP/GADD153, that can induce apoptosis. Although eIF2P elicits translational control in response to many different stress arrangements, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2P. In this study we addressed the underlying mechanism for variable expression of ATF4 in response to eIF2P during different stress conditions and the biological significance of omission of enhanced ATF4 function. We show that in addition to translational control, ATF4 expression is subject to transcriptional regulation. Stress conditions such as endoplasmic reticulum stress induce both transcription and translation of ATF4, which together enhance expression of ATF4 and its target genes in response to eIF2P. By contrast, UV irradiation represses ATF4 transcription, which diminishes ATF4 mRNA available for translation during eIF2∼P. eIF2P enhances cell survival in response to UV irradiation. However, forced expression of ATF4 and its target gene CHOP leads to increased sensitivity to UV irradiation. In this study, we also show that C/EBPβ is a transcriptional repressor of ATF4 during UV stress. C/EBPβ binds to critical elements in the ATF4 promoter resulting in its transcriptional repression. The LIP isoform of C/EBPβ, but not the LAP version is regulated following UV exposure and directly represses ATF4 transcription. Loss of the LIP isoform results in increased ATF4 mRNA levels in response to UV irradiation, and subsequent recovery of ATF4 translation, leading to enhanced expression of its target genes. Together these results illustrate how eIF2P and translational control, combined with transcription factors regulated by alternative signaling pathways, can direct programs of gene expression that are specifically tailored to each environmental stress.
Palam, Lakshmi Reddy. "REGULATION OF CHOP TRANSLATION IN RESPONSE TO eIF2 PHOSPHORYLATION AND ITS ROLE IN CELL FATE." Thesis, 2012. http://hdl.handle.net/1805/3182.
Повний текст джерелаIn response to different environmental stresses, phosphorylation of eukaryotic initiation factor-2 (eIF2) rapidly reduces protein synthesis, which lowers energy expenditure and facilitates reprogramming of gene expression to remediate stress damage. Central to the changes in gene expression, eIF2 phosphorylation also enhances translation of ATF4, a transcriptional activator of genes subject to the Integrated Stress Response (ISR). The ISR increases the expression of genes important for alleviating stress, or alternatively triggering apoptosis. One ISR target gene encodes the transcriptional regulator CHOP whose accumulation is critical for stress-induced apoptosis. In this dissertation research, I show that eIF2 phosphorylation induces preferential translation of CHOP by a mechanism involving a single upstream ORF (uORF) located in the 5’-leader of the CHOP mRNA. In the absence of stress and low eIF2 phosphorylation, translation of the uORF serves as a barrier that prevents translation of the downstream CHOP coding region. Enhanced eIF2 phosphorylation during stress facilitates ribosome bypass of the uORF, and instead results in the translation of CHOP. Stable cell lines were also constructed that express CHOP transcript containing the wild type uORF or deleted for the uORF and each were analyzed for expression changes in response to the different stress conditions. Increased CHOP levels due to the absence of inhibitory uORF sensitized the cells to stress-induced apoptosis when compared to the cells that express CHOP mRNA containing the wild type uORF. This new mechanism of translational control explains how expression of CHOP and the fate of cells are tightly linked to the levels of phosphorylated eIF2 and stress damage.
Guang-Yau, Yee, and 易光燿. "Protein-DNA Interactions in the Transcriptional Regulation of Eukaryotic Genes." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/42651704630628579724.
Повний текст джерела國防醫學院
生物化學研究所
86
Thymidine kinase, a crucial enzyme in the salvage pathway of thymidine triphosphate formation, is involved in the process of DNA replication. The level of thymidine kinase(TK) is known to be increased at the G1/S phase of the cell cycle. Transcriptional activation is important for the increase of human thymidine kinase(hTK) expression at the G1/S phase of the cell cycle . In this study, in order to examine the DNA sequence responsible for the transcriptional activation of hTK gene in young cells during growth stimulation and transcriptional repression in old ones, the interaction between nuclear protein factors and hTK promoter was examined by in vivo footprinting in young and old IMR-90 cells, respectively. Results from in vivo footprinting of hTK promoter in young and old IMR-90 cells showed that NF-Y binding sites could be one of key cis-elements responsible for transcriptional activation of hTK gene. In addition, in vivo footprints of old IMR- 90 cells on the DNA sequence between two adjacent NF-Y binding sites, CCAAT boxes, were apparently different from those of young cells. Thus, CCAAT-binding proteins might be associated ageing. On the other hand, in order to understand the molecular basis underlying the E1A-mediated transcriptional repression of the c-erbB-2 overexpression in human cancer cells, we compared the nuclear factor-binding patterns of c-erbB-2 promoter in vivo in cell lines with and without exogenous E1A expression. However, we did not observe any difference of nuclear factor-binding in vivo of E1A-non-expressing cells versus E1A-expressing cells. Therefore, E1A might repress the transcriptional overexpression of c-erbB-2 gene through protein-protein interactions with some endogenous factors. Furthermore, in order to show the correlation between the distribution of Sp1 elements and the demethylation patterns in the CpG islands of the human globin gene, we have analyzed the methylation patterns of human globin promoter and its interaction with Sp1 factor by genomic sequencing and in vivo footprinting, respectively. HeLa cells with high passage number didn't show significant protein- DNA interactions at Sp1 binding sites within the human globin gene as K562 cells did and its genomic DNA was highly methylated downstream of the cap site (+1). This indicated that Sp1 sites in human adult globin gene promoters might correlate to demethylation of erythroid-specific CpG islands.