Thèses sur le sujet « Modification de l'ADN »
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Rio, Pascale. « Role du polymorphisme de l'adn en cancerogenese chimique : modification de l'adn par deux derives de l'acetylaminofluorene ». Orléans, 1989. http://www.theses.fr/1989ORLE2027.
Texte intégralCiroussel, Françoise. « La cancerogenèse par le chlorure de vinyle : modification de l'ADN et dosimétrie moléculaire ». Lyon 1, 1990. http://www.theses.fr/1990LYO10057.
Texte intégralSpadiliero, Barbara. « Epigenetic traits in the parasite Trypanosoma cruzi : DNA and histones modifications linked to its life cycle ». Paris 6, 2009. http://www.theses.fr/2009PA066759.
Texte intégralBELGUISE-VALLADIER, PASCALE. « Etude de la modification de l'adn par un cancerogene, le n-2-acetylaminofluorene : etudes structurales et consequences biologiques ». Strasbourg 1, 1993. http://www.theses.fr/1993STR13204.
Texte intégralBougueleret, Lydie. « Contribution à l'étude des systèmes de restriction modification EcoR I et EcoR V ». Paris 7, 1985. http://www.theses.fr/1985PA077010.
Texte intégralFonteneau, Mathieu. « La modification de la méthylation de l'ADN régule le comportement d'auto-administration de cocaïne chez le rat : caratérisation des gènes impliqués ». Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ059/document.
Texte intégralRepeated drug administration lead to pathological brain plasticity that requires modifications of gene expression through, among others, epigenetic mechanisms such DNA methylation. Here, we showed that DNA methyltransferases inhibitors such 5-aza-2’-deoxycytidine increase reinforcing properties of cocaine in an intravenous self administration paradigm without affecting the motivation of rats for the drug, nor drug seeking after withdrawal. The analysis of the methylome in the medial prefrontal cortex allowed us to identify approximatively 190000 differentially methylated genomic regions in response to cocaine treatment, in association or not with 5-aza-2’-deoxycytidine. We selected around twenty regions within promoters or body of genes known to participate in neuronal plasticity. The study of the transcription of these genes permitted for some of them to correlate the modifications of the DNA methylation with the modifications of the expression, like, for example, in the case of the gene Hdac2
Heberle, Eléa. « Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN ». Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ106.
Texte intégralPoly (ADP-ribosyl) ation is a post-translational modification of proteins involved in a large number of biological processes, including DNA repair. While the function and mode of action of Poly (ADP-ribose) (PAR) Polymerase 1 (PARP1), activated in response to DNA damage, is well understood, much less is known about the function and regulation the PAR degrading enzyme, Poly (ADP-ribose) glycohydrolase (PARG). In the context of this thesis project, we describe new stable U2OS lines, deficient for all PARG isoforms, allowing the inducible complementation with each of the PARG isoforms. These models allowed us to evaluate the relative contributions of the isoforms to DNA damage repair. We have identified a new cellular partner of PARG: the DNA-dependent protein kinase-dependent kinase (DNA-PK). We explore the functional interaction between these two proteins in the context of the cellular response to camptothecin (CPT), an anticancer drug that inhibits topoisomerase I and induces the simultaneous activation of PARP1 and DNA-PK
Malytska, Iuliia. « Exploring bipolar electrochemistry for the modification of unusual conducting substrates ». Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0135/document.
Texte intégralBipolar electrochemistry is a phenomenon based on the polarization of conductive objects in an electric field. In contrast to conventional electrochemistry, the drop of potential in the electrolyte solution triggers the involved redox reactions. When a conductive object is positioned in an electric field present in a solution between two feeder electrodes, it is polarized and becomes a bipolar electrode. The potential difference between the electrolyte and the bipolar electrode is the driving force for reduction/oxidation reactions at the two extremities of the bipolar electrode; oxidation will occur at one end, combined simultaneously with reduction at the other end.Bipolar electrochemistry is a concept that allows generating an asymmetric reactivity at the surface of a conductive object. During the last decade, bipolar electrochemistry found many applications such as the synthesis of asymmetric micro- and nano-particles, electrodeposition, sensing, propulsion of microobjects, electroanalysis etc. The advantage of this technique is its wireless character, which allows the modification of delicate materials and also to electrochemically address many objects simultaneously.In the present thesis, the approach was applied to different semiconducting materials and biological systems. In addition, properties of substrates of different nature have been studied using bipolar electrochemistry.In this way, it was possible to create metal deposits on organic charge transfer salts in a site-specific way. The resulting hybrid metal/organic particles were tested for the asymmetric generation of photovoltage under illumination.Inorganic transition metal dichalcogenides were also used as a substrate for bipolar electrochemistry. Deposition of different metals on MoSe2 macroparticles was performed. Transition metal dichalcogenides are known for their catalytic activity with respect to hydrogen evolution reaction. Therefore, wireless hydrogen production on MoSe2 crystals and microparticles could be demonstrated by using bipolar electrochemistry. In the latter case it is possible to envision their use for electrochemical decontamination of solutions in the bulk.Finally, bipolar electrochemistry has also been used for studying the conductivity of biological molecules (DNA). The primary goal was to develop a new approach for the asymmetric modification of DNA by metal nanoparticles. Experiments were performed by using either Capillary Assisted Bipolar Electrodeposition (CABED) with the DNA molecules present in the bulk, or by immobilizing DNA as stretched entities on model surfaces for subsequent modification. Encouraging first results could be evidenced by TEM or AFM measurements
Hu, Guojian. « Hormonal and epigenetic control of pollination-dependent and pollination-independent fruit-setting in tomato ». Phd thesis, Toulouse, INPT, 2017. http://oatao.univ-toulouse.fr/18575/1/HU.pdf.
Texte intégralEl, Khoury Victoria Dufer Jean. « Etude de modifications épigénétiques corrélées à l'expression du gène MDR1 et à la texture nucléaire dans des cellules de carcinome pulmonaire H69 sensibles et résistantes à la chimiothérapie ». S.n. : S.l, 2006. http://scdurca.univ-reims.fr/exl-doc/GED00000322.pdf.
Texte intégralChoofong, Surakarn. « DNA damage induced by low energy electrons (LEEs) ». Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/8873.
Texte intégralRésumé: L'objectif majeur de ce projet étude est d'étudier les lésions d'ADN induites par les rayons X mous (1,5 keV) et des électrons de faible énergie (˂ 30 eV) à partir d'un nouveau système d'irradiation créé par le groupe du Pr. Sanche. De minces couches d'ADN double brin sont déposées soit sur du verre ou sur les substrats de tantale. Celles-ci sont irradiées sous une température et pression environnante, mais dans une atmosphère de N[indice inférieur 2]. Les bases relâchées (cytosine, la thymine, l'adénine et la guanine) et les produits de modification de base (8-oxo-7,8-dihydro-2'-désoxyguanosine, 5-hydroxyméthyl-2'-désoxyuridine, 5-formyl-2'-désoxyuridine, 5,6-dihydrothymine et 5,6-dihydrouridine) sont analysés et quantifiés par LC-MS/MS. Nos résultats révèlent un plus grand rendement de dommages dans les échantillons déposés sur le tantale que celles sur le verre. Cette différence peut être expliquée par l’interaction des électrons de faible énergie qui sont photo émis des substrats métalliques. D'après les résultats obtenus, la libération de bases est un produit majeur en comparaison avec la modification de bases. Ceci provient, en particulier, surtout des purines qui libèrent la base a un niveau trois fois plus grand que la modification de la base. Une voie proposée, conduisant à la libération de base, implique la formation d'ions négatifs transitoires (TNI), suivie par l'attachement d'électrons dissociatifs (DEA) à la liaison N-glycosidique. En outre, les produits de modification de base sont composés en deux grands types de modifications chimiques. L’un des produits est l’oxydation du groupe méthyle de la thymine, qui probablement consiste de en d'hydrure (-H[indice supérieur -]) par l'intermédiaire de DEA. Alors que l’autre modification chimique est la formation de 5,6-dihydropyrimidine qui implique l'addition d'hydrure à la double liaison du 5,6-pyrimidine.
Yi, Jia. « The Role of Convergent Transcription in Regulating Alternative Splicing : Targeted Epigenetic Modification via Repurposed CRISPR/Cas9 System and Its Impact on Alternative Splicing Modulation ». Electronic Thesis or Diss., Sorbonne université, 2020. http://www.theses.fr/2020SORUS382.
Texte intégralAlternative splicing of precursor RNA is a co-transcriptional process that affects the vast majority of human genes and contributes to protein diversity. Dysregulation of such process is implicated in various diseases, including tumorigenesis. However, the mechanisms regulating these processes were still to be characterized. In this study, we showed that perturbations of alternative splicing correlated with dysregulations of convergent transcription and DNA methylation. Convergent transcription could be generated between pairs of neighboring genes in opposite orientation, or between intragenic enhancers and their host gene. CENPO and ADCY3 was identified as a convergent transcription gene pair. We found, in a tumor progression model of breast cancer, that the splicing change of the ADCY3 variant exon22 correlated with an increase of its transcription that went against that of CENPO. By using targeted transcription repression system CRISPRi, we demonstrated that downregulating the transcription of CENPO could not reverse the alternative splicing alteration of ADCY3 in cancer cells (DCIS). An active intragenic enhancer was identified in the intron16 of CD44, at the downstream of its alternative exons. By using targeted transcription activation system CRISPRa, we showed that upregulating the transcription of CD44 could not alter the alternative splicing of CD44 in DCIS cells. These results suggest that convergent transcription modulation through changes of promoter activity does not alter the alternative splicing of ADCY3 and CD44 in DCIS cells. However, through replacing the intragenic enhancer by an inducible promoter, we found that intragenic transcription activation increased the inclusion level of several alternative exons of CD44 in HCT116 cells. This result suggested that local convergent transcription could have a direct impact on the alternative splicing of CD44. Furthermore, by using targeted DNA methylation system CRISPR/dCas9-DNMT3b, we showed that DNA methylation at variant exons could directly modify CD44 alternative splicing. This thesis work also explored the limitation and feasibility of studying alternative splicing with repurposed CRISPR systems
Perriaud, Laury. « Étude systémique des cibles génomiques de la methyl-CpG binding domain protein 2 (MBD2), un répresseur transcriptionnel dépendant de la méthylation de l'ADN : évolution de la distribution de MBD2 dans un modèle syngénique de progression tumorale mammaire ». Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00833153.
Texte intégralBarbe, Sophie. « Modulation de l'interaction intégrase/ADN du VIH-1 par des dérivés des styrylquinoléines et par la modification de nucléotides ». Phd thesis, École normale supérieure de Cachan - ENS Cachan, 2006. http://tel.archives-ouvertes.fr/tel-00129455.
Texte intégralSUN, LI-YAN, et Arlette Nougarède. « Etude de la modification du programme de la mise a fleurs et du phenotype chez le tabac, la carotte et l'endive sous l'influence de genes provenant de l'adn-tl du plasmide ri de la souche a4 d'agrobacterium rhizogenes ». Paris 6, 1991. http://www.theses.fr/1991PA066642.
Texte intégralLe, Ber Pierre. « Utilisation d'un marqueur de spin, le proxyl-opc, pour des experiences de competition en rpe. Modification par deux analogues structuraux, l'opc et le pentyl-opc, de l'equilibre b-z in vitro. Degradation oxydative de l'adn par la riboflavine irradiee dans le visible ». Paris 11, 1990. http://www.theses.fr/1990PA112127.
Texte intégralHognon, Cecilia. « Modélisation et simulation moléculaire pour la compréhension des processus biologiques fondamentaux et le développement de nouveaux agents thérapeutiques contre le cancer et la Covid-19 ». Electronic Thesis or Diss., Université de Lorraine, 2021. http://www.theses.fr/2021LORR0233.
Texte intégralDuring this Ph.D. thesis I have used state-of-the-art molecular modeling and simulation techniques to answer to key biological questions related to the fundamental bases of cancer development and to the mechanisms of viral replication and diffusion, including those of SARS-CoV-2. In addition to rationalize the molecular bases behind critical biological outcomes, including also the assessment of the thermodynamic properties of key biological aggregates, I have also studied the possible rational molecular design of novel therapeutic agents acting as antiviral and anticancer. To this end I have studied the induction and reparation of DNA lesions, as well as the basis of genome organization and DNA compaction. This has also brought me to take into accounts epigenetic regulation, the possible design of external agents perturbing gene expression, and the regulation of signaling pathways such as iron homeostasis. Furthermore, I have studied key viral components of SARS-Cov-2 including the spike protein, some non structural proteins such as the SARS Unique Domain, and the organization of its genome, for the formation of guanine quadruplexe sequences. Furthermore, I have also been interested in the understanding of immune system response, and in particular on the effects of variants on the human STING protein, which is able to sense the presence of endogenous genetic material and triggers the appropriate immune response. From a methodological point of view the use of multiscale approach, combining in some instance classical and QM/MM methods have shown its power in rationalizing not only chemical but biological effects and has paved the way to stronger rational design strategies
Siouda, Maha. « Transcriptional regulation and epigenetic repression of the tumor suppressor DOK1 in viral- and non viral-related carcinogenesis ». Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10163.
Texte intégralThe newly identified tumor suppressor DOK1 (downstream of tyrosine kinases1) inhibits cell proliferation, negatively regulates MAP kinase activity, opposes leukemogenesis, and promotes cell spreading, motility, and apoptosis. DOK1 also plays a role in the regulation of immune cell activation, including B cells. The tumor suppressor role of DOK1 was demonstrated in animal models. DOK1 knockout mice show a high susceptibility to develop leukemia, hematological malignancies as well as lung adenocarcinomas and aggressive histiocytic sarcoma. In addition, we previously reported that the DOK1 gene can be mutated and its expression is down-regulated in human malignancies such as Burkitt’s lymphoma cell lines (BL) and chronic lymphocytic leukemia (CLL). However, very little is known about the mechanisms underlying DOK1 gene regulation and silencing in viral- and non viral-related tumorigenesis. In the present project, we first characterized the DOK1 promoter. We have shown the role of E2F1 transcription factor as the major regulator of DOK1 expression and how DOK1 plays a role in DNA stress response though opposing cell proliferation and promoting apoptosis. We demonstrated that DOK1 gene expression is repressed in a variety of human cancers, including head and neck, Burkitt’s lymphoma and lung cancers, as a result of aberrant hypermethylation. We investigated the link between the epigenetic events and DOK1 silencing in non viral head and neck cancer cell lines, and by Epstein Barr virus in relation to its oncogenic activity in human B cells and neoplasia such as Burkitt’s lymphoma. These data provide novel insights into the regulation of DOK1 in viral and non viral-related carcinogenesis, and could define it as a potential cancer biomarker and an attractive target for epigeneticbased therapy
Lhaneche, Leila. « Modifications génétiques et épigénétiques et régulation de l'expression du gène SOSTdans l'os humain ». Paris 7, 2013. http://www.theses.fr/2013PA077144.
Texte intégralSOST encodes sclerostin, an inhibitor of bone formation produced by osteocytes that antagonizes canonical Wnt signaling and bone formation. Variations of SOST expression have an impact on bone mineral density (BMD) and bone strength. My thesis goal was to find out how natural DNA modifications, genetic and epigenetic, are able to modulate gene expression in human bone samples and modify bone phenotype in human diseases. In one hand we showed that rs851054 polymorphism located in SOST promoter is associated with SOST expression variation in trabecular bone samples of 56 healthy individuals, and in the other hand we showed that fracture rate and BMD in 131 patients with osteogenesis imperfecta (OI), which is a rare disease characterized by low BMD and bone fragility. Besides, we also investigated the role of CpG methylation in SOSTmKNA expression, and analyzed methylation variation at 13 CpG sites on the 1st exon ofSOST in 14 human bone samples. We found that decrease in DNA methylation is correlated with decrease in SOSTgene expression. In conclusion, we showed that genetic and epigenetic variation of the SOST gene ma> contribute to change in SOST expression SOST expression in human bone. Our data also indicate that variations in SOS1% expression may be related to the severity of OI
Caillet, Joël. « L'arn de transfert d'escherichia coli specifique de la phenylalanine : biosynthese et modification ». Paris 7, 1991. http://www.theses.fr/1991PA077144.
Texte intégralElhadad, Sonia. « L'adressage de l'hélicase du syndrome de Bloom, BLM, aux sites de réparation de l'ADN, est régulé par SUMO ». Montpellier 2, 2005. http://www.theses.fr/2005MON20046.
Texte intégralSamson-Thibault, François. « Analyse des modifications de la cytosine après oxydation de l'ADN par digestion enzymatique et HPLC-MS/MS ». Mémoire, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6359.
Texte intégralMalouf, Gabriel. « Décryptage des changements épigénétiques impliqués dans la transition épithélio-mésenchymateuse et le cancer ». Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T037.
Texte intégralThe epithelial-Mesenchymal transition (EMT) is a process of cellular plasticity that exists in embryonic development and which allows the formation of tissues and organs. In carcinogenesis, the process is reactivated by transcription factors whose action probably involves chromatin remodeling. The exact mapping of these epigenetic changes is poorly understood genome-Wide, although there have been some previous studies exploring changes in so few well-Targeted loci. This thesis deals with the epigenetic remodeling mediated by the transcription factor Twist1 in a model of human mammary immortalized cell line. The architecture of this remodeling has been mapped through the use of high-Throughput techniques to analyze DNA methylation (DREAM) and histone modifications (ChIPseq). Our results suggest a major change in the EMT methylome with focal hypermethylation and gene body hypomethylation predominantly within "partially methylated domains"; these areas are already known in development to gain repressive histone marks concomitantly with DNA hypomethylation. We also observed landscape remodeling of repressive histone mark H3K27me3 with a reduction in domains size, and especially the almost doubling of the number of bivalent genes. The coupling of DNA methylation with the profile of microRNA has allowed us to identify miR-203 as single microRNA regulated by DNA methylation during EMT; we have also shown that epigenetic suppression of miR-203 is both required for EMT and acquisition of stem cell properties. Finally, we performed a genetic and/or epigenetic characterization of two rare cancers, named fibrolamellar hepatocellular carcinomas and translocation renal cell carcinomas. In fibrolamellar hepatocellular carcinoma, we described the endocrine nature of this tumor and established a signature based on DNA methylation which can be used to distinguish histological forms called "pure" from "mixed" fibrolamellar hepatocellular carcinomas. Regarding translocation renal cell carcinomas, we established the genetic and epigenetic basis of differences between pediatric and adult forms, characterized by frequent gain of 17q gain chromosomal arm in adults. We also identified recurrent mutations in the chromatin remodeling gene INO80D which belongs to INO80 family. In conclusion, this work explores the impact of analyzing the epigenome to understand reprogramming during physiological processes such as EMT and cancer
Kress, Clémence. « Régulation de la mémoire épigénétique : la dynamique de la méthylation de l'ADN et son couplage aux modifications de la chromatine ». Paris 6, 2004. http://www.theses.fr/2004PA066179.
Texte intégralLafont, Florian. « Implication des modifications post-traductionnelles de DNA-PKcs dans la régulation de la réponse aux dommages à l'ADN ». Thesis, Nantes, 2017. http://www.theses.fr/2017NANT1023/document.
Texte intégralHuman cells are subjected to stresses inducing DNA double-strand breaks mainly repaired by the NHEJ pathway, where the kinase DNA-PKcs plays a central role. The activity of DNA-PKcs, regulated by numerous phosphorylations, is crucial for the maintenance of genomic integrity. More recently, it has been shown that this protein is also modified by O-GlcNAcylation in the COS7 cell line. Knowing the balance between phosphorylation and O-GlcNAcylation, we studied the role of this new PTM in the regulation of DNA-PKcs activity. We have shown that DNA-PKcs is O-GlcNAcylated in HeLa cells. We then showed that the modulation of DNA-PKcs O-GlcNAcylation affects its autophosphorylation on Ser2056, suggesting an O-GlcNAcylation/phosphorylation balance, as well as the ability of cells to repair DSBs by NHEJ pathway. Moreover, our results allow us to consider that this modification may play a role in protein stability. DNA-PKcs is a potential target in anticancer strategies. We studied the impact of a chemical compound on DNA-PKcs activity. This molecule causes a reduction in the amount and activity of DNA-PKcs, through its ubiquitinylation and its degradation by the proteasome and leading to sensitization of the cells to genotoxic treatment. In this context, we have developed an antibody microarray to evaluate the phosphoprotein level of DNA repair pathways and thus estimate the effect of DNA-PKcs inhibitors. All these results contribute to a better understanding of the regulation of DNA-PKcs
Tyteca, Sandrine. « Rôle de l'histone acétyltransférase Tip60 dans la réponse aux dommages à l'ADN ». Toulouse 3, 2008. http://thesesups.ups-tlse.fr/276/.
Texte intégralTip60 is a histone acetyltransferase acting as as a multimolecular complex in the cell : the so-called Tip60 complex. It is involved in several cellular processes such as proliferation, apoptosis and DNA damage response. As far as the latter aspect is concerned, we showed that Tip60 is involved in the p53 tumour suppressor pathway in response to DNA damage. Then we showed that Tip60 is required for apoptosis and cell cycle arrest in response to UV irradiation, and revealed a functional antagonism between Tip60 and p400, another subunit of the Tip60 complex. We also recently discovered that Tip60 is involved in homology-driven double-strand break repair. We showed an interaction between Tip60 and the MRN complex which allows the recognition of double-strand breaks in DNA. Our results suggest that the Tip60/MRN complex could be the one responsible for the ATM kinase activation in response to double-strand breaks. Altogether, our results contributed to show the crucial role of Tip60 at multiple levels of the DNA damage response : damage signaling, DNA repair, cell cycle arrest and apoptosis
Descostes, Nicolas. « Analyse bioinformatique des modifications post-traductionnelles du domaine carboxyl-terminal de l'Arn polymérase II ». Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4089.
Texte intégralThe biggest subunit of eukaryotic RNA polymerase II contains a carboxy-terminal domain (CTD) that consists in a repetition of seven amino-acids ranging from 26 in yeast to 52 in mammals. Specific biochemical modifications of CTD residues have been linked to specific stages of the transcriptional process. The CTD acts as a recruitment platform for processing factors that are involved in initiation, promoter proximal pausing, early and productive elongation (alternative splicing), 3' processing, termination and epigenetics.During my PhD, I used bioinformatics and high-throughput sequencing data to study two novel biochemical modifications of the CTD in human. I showed, in collaboration with biologists and bioinformaticians, that threonine 4 phosphorylation is important for proper elongation and probably termination of transcription. I showed also that tyrosine 1 phosphorylation is present during early transcription, antisense transcription (at divergent promoters) and is hyperphosphorylated at transcribed and tissue specific enhancers.Overall my doctorate has contributed to the understanding of the transcriptional process in human through the use of innovative bioinformatic methods
Masmoudi, Ahmed. « Etude de l'ADP-ribosylation dans les mitochondries ». Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37615884v.
Texte intégralTaty, Taty Gemael Cedrick. « Rôle des modifications de la chromatine dans la réparation des cassures double-brin de l'ADN et la stabilité génétique ». Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30190/document.
Texte intégralThe human genome is constantly targeted by DNA damaging agents. These damages are many and varied, such as single and double strand breaks (DSBs). The DSB are highly toxic lesions whose origin can be multiple. Mammalian cells mainly use two DNA repair pathways to repair DSB, homologous recombination (RH), which is dependent on the presence of the intact homologous copy (the sister chromatid) and on the cell cycle stage and the non-homologous end joining (NHEJ) pathway, which is cell cycle independent and performs direct ligation of the two DNA ends. The repair of DNA damage takes place in a chromatin context that needs to be remodeled to give access to damaged sites. During my work, I studied the chromatin remodeler p400 and the histone variant H2A.Z both involved in chromatin remodeling, to understand their role in DSB repair and genome stability. p400, an ATPase of the SWI2/SNF2 family is involved in the incorporation of H2A.Z in chromatin. I have shown that H2A.Z depletion in the osteosarcoma cell line U2OS and in immortalized human fibroblasts did not alter DSB repair. These results are correlated with the lack of H2A.Z recruitment at DSB observed after local laser irradiation or Chromatin Immunoprecipitation. However, H2A.Z depletion affects cell proliferation and the cell cycle distribution. In addition, I have shown that the chromatin remodeler p400 is a brake to the use of alternative End Joining (alt-EJ) which is a highly mutagenic repair process. The increase in alt-EJ events observed in p400-depleted cells is dependent on CtIP- mediated resection of DNA ends. Moreover, p400 depletion leads to the recruitment of poly(ADP) ribose polymerase (PARP) and DNA ligase 3 at DSB, leading to selective cell killing by PARP inhibitors. Altogether these results show that p400 acts as a brake to prevent alt-EJ dependent genetic instability and underline its potential value as a clinical marker
Thiebaut, Frédéric. « Photomarquage d'affinité couplé à la spectrométrie de masse pour l'identification de protéines interagissant avec des modifications épigénétiques de l'ADN ». Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066490/document.
Texte intégralOver the past few decades, DNA methylation at the 5-position of cytosine has emerged as an important epigenetic modification that plays essential roles in the specific control of gene expression. However, the mechanisms involved in the regulation of DNA methylation remain unclear. Recent studies have shown that oxidase proteins, called TETs, can catalyze the oxidation of 5-methylcytosine (5 mC) and generate oxidized derivatives thereof, raising the question of the biological role of the oxidized forms of 5mC. The identification and characterization of proteins interacting with these oxidized forms should allow for a better understanding of the function of these DNA modifications and the regulation of DNA methylation.In this project, we develop DNA-based photoactivatable probes to capture, isolate and characterize the proteins associated with these epigenetic DNA modifications. First, we designed and evaluated the properties of different photoactivatable oligonucleotide probes. We then carried out a methodological study in order to characterize at the molecular level the obtained photoadducts by MALDI-TOF. Finally, we developed a pull-down method coupled to photolabelling and associated with proteomic analysis by mass spectrometry to identify proteins with specific affinity for these epigenetic changes
Adjakly, Mawussi. « Modifications épigénétiques de la méthylation de l'ADN induites par les phyto-oestrogènes du soja dans le cancer de la prostate ». Thesis, Clermont-Ferrand 1, 2012. http://www.theses.fr/2012CLF1MM22.
Texte intégralProstate cancer is a disease caused by a multiple interacting factors such as family history of prostate cancer, age and ethnic origin. Environnemental factors play also a role in prostatic carcinogenesis events. Indeed, several studies have reported the efficiency of nutrients such as phytoestrogens to possess anticancer properties. It has been reported that these compounds may have the ability to induce the reversion of epigenetic modifications observed in prostate cancer cells. The aim of this work was to determine if soy isoflavone could reverse the DNA methylation of oncosuppressor which are hypermethylated in prostate cancer and through which metabolic pathways. Our in vitro studies were carried out on tree prostate cancer cell lines: DU-145, PC-3 and LNCaP. The qualitative and quantitative studies performed demonstrated a decrease of methylation percentage of GSTP1, RASSF1A, EPHB2 and BRCA1 after soy isoflavone treatment. In a second step, a comparative study between the effect of phytoestrogens and estradiol on the DNA methylation of a panel of 24 genes was performed. Our results has highlighted that the regulation of epigenetic mechanisms by phytoestrogens may be mediated via the estrogen receptor pathway. In conclusion, phytoestrogen act on epigenetics mechanisms on prostate carcinogenesis suggesting that these molecules may play a role in the prevention of this pathology
Cong, Rong. « Functional analysis of nucleolin-chromatin interaction in vivo ». Thesis, Lyon, École normale supérieure, 2011. http://www.theses.fr/2011ENSL0636.
Texte intégralBesides the well-known role of the nucleolus in ribosome biogenesis, nucleoli play important roles in the regulation of many fundamental cellular processes, including cell cycle regulation, apoptosis, telomerase production, RNA processing and therefore it is not surprising that many nucleolar proteins appear to be multifunctional proteins. Nucleolin, one of the most abundant non-ribosomal proteins of the nucleolus, has been the focus of many studies since it was first described 35 years ago. It seems to be involved in many aspects of DNA metabolism, chromatin regulation and appeared to be a good pharmacological target for drug development in addition to its role in RNA polymerase I transcription and pre-ribosomal processing and assembly in pre-ribosomes. In eukaryotic cells, DNA is packed into nucleosomes to form chromatin in the nucleus. The cells develop a variety of strategies to overcome the nucleosomal barriers. These strategies include DNA methylation, histone post-translational modifications, incorporation of histone variants and ATP dependent chromatin remodeling. The aim of this thesis is to study the interaction of nucleolin with chromatin, and to decipher the mechanism of nucleolin in gene regulation. It was reported that nucleolin possesses a histone chaperone activity, helps the transcription through nucleosomes, and it is required for ribosomal DNA gene (rDNA) transcription in vivo, but the mechanism by which nucleolin modulates RNA polymerase I (Pol I) transcription is unknown. In the thesis it is shown that nucleolin knockdown results in an increase of the heterochromatin mark H3K9me2 and a decrease of H4K12Ac and H3K4me3 euchromatin histone marks in rDNA genes. Nucleolin is associated with unmethylated rDNA genes and ChIP-seq experiments identified a strong enrichment of nucleolin in the promoter and coding regions of rDNA. Nucleolin is able to interfere with the binding of TTF-1 on the promoter-proximal terminator T0 thus inhibiting the recruitment of the nucleolar remodeling complex (NoRC) subunit TIP5 and HDAC1 and the establishment of a repressive heterochromatin state. In addition, in absence of nucleolin or after inhibition of Pol I by actinomycin D, a strong relocalization of the histone variant macroH2A1 to the nucleolus and on the rDNA genes was observed. This invasion of macroH2A1 in the nucleolus plays a major role in the inhibition of Pol I transcription in absence of nucleolin, as knockdown of macroH2A1 eliminates the repressive effect of nucleolin depletion. These results reveal the importance of nucleolin for the maintenance of the euchromatin state of rDNA required for an efficient production of ribosomal RNAs and the role of macroH2A1 in rDNA transcription
Marion-Poll, Lucile. « Modifications épigénétiques et transcription dans les deux types de neurones épineux de taille moyenne du striatum ». Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066172.
Texte intégralThe striatum is a brain region implicated in physiological functions such as reinforcement learning or movement selection but also in pathologies such as addiction or Parkinson’s disease. It relies on two types of projecting neurons, named “medium spiny neurons” because of their morphology. They are very similar but have a complementary and opposite role. One type expresses the dopamine receptor type 1 (D1R) and the other type expresses the dopamine receptor type 2 (D2R). The aim of this work was to characterize this two neuronal types epigenetically, in basal conditions and after cocaine treatment. We have developed new flow cytometry techniques to be able to distinguish the two cell types. The first method uses transgenic L10-eGFP mice and fresh tissue, the second one goes beyond the limitations of the first one and uses fixed tissue. We have shown that cocaine regulates many post-translational histone modifications, dynamically, and differently between the two populations. Moreover, we have identified more than 100 genes differentially methylated or hydroxymethylated between the two neuronal types. Some of these genes are already known for having a functional role in one of the populations. The comparison between D1R and D2R neurons is a good model to explore the links between DNA methylation, hydroxymethylation and transcription. For example, we have observed a strong association between an increase in DNA methylation and a transcriptional repression, as well as a correlation between DNA methylation and hydroxymethylation
Ousset, Marielle. « Lien entre la signalisation des dommages de l'ADN et l'adaptation cellulaire à l'hypoxie : deux nouveaux rôles pour ATM (Ataxia Telangiectasia Mutated) et DNA-PK (protéine Kinase dépendante de l'ADN) ». Toulouse 3, 2010. http://thesesups.ups-tlse.fr/907/.
Texte intégralHypoxia is a frequent microenvironmental stress observed in human tumours. The key regulator of the cellular response to oxygen deprivation is the transcription factor, HIF-1 (Hypoxia Inducible Factor 1) whose function resulting in the induction of a plethora of target genes that collectively confers cellular adaptation to hypoxia. HIF-1 is comprised of an alpha sub-unit that is mainly targeted for degradation in normoxia whereas its beta sub-unit is constitutively expressed. Emerging evidences suggest that hypoxia induce a DNA damage response (DDR). However, the mechanism involved in the initiation of this DDR and the consequences of its activation are unknown. The goal of our project was to investigate the role of two proteins, which are involved in DDR belonging to the PI3KKs (Phosphatidyl Inositol 3 Kinase Like Kinase) family, ATM and DNA-PK, in the hypoxic response. We studied their activation and the consequences on HIF-1 accumulation in these conditions. So as a first step, we have demonstrated that the loss of ATM positively regulates the expression of both sub-units of HIF-1, in normoxia and hypoxia. Besides its role in the cellular adaptation to hypoxia, this effect might be important to explain some clinical features of Ataxia Telangiectasia, the disease associated to the mutation of ATM gene in humans. Moreover, we observed ATM activation in severe hypoxia (less than 0. 1% O2), with no consequences on HIF-1 accumulation. On the other hand, we have reported that DNA-PK, involved in double strand breaks (DSBs) signalling and repair, is activated in mild hypoxic conditions (less than 1 % O2). Our results suggest that its activation is independent from DSBs. Hypoxia is associated to histones modifications including acetylation and we demonstrated that these chromatin modifications are responsible for DNA-PK activation in hypoxic conditions. Finally, we have demonstrated that once activated DNA-PK regulates the stability of HIF-1alpha, promoting the cellular adaptation to hypoxia. Taken together, our results show a role of PI3KKs in HIF-1 regulation and suggest that hypoxia initiates DNA damage like-response, contributing to the adaptative response of cells to hypoxic conditions
Mestre, Béatrice. « Préparation de molécules conjuguées "oligonucléotide-métalloporphyrine" : influence de modifications structurales sur leur activité nucléasique vis-à-vis de l'ADN simple brin ». Toulouse 3, 1996. http://www.theses.fr/1996TOU30267.
Texte intégralFleury-Ricordeau, Laurence. « Modifications épigénétiques dans le cancer du sein ». Toulouse 3, 2008. http://thesesups.ups-tlse.fr/301/.
Texte intégralIn breast cancer, approximately one third of tumors express neither the estrogen receptor (ERa) nor estrogen regulated genes such as the Progesterone Receptor gene (PR). Our study provides new insights into the mechanism allowing hormone-activated expression of ERa target genes silenced in ERa-negative mammary tumor cells. In cell lines derived from ERa-negative MDA-MB231 cells, stable expression of different levels of ERa from a transgene did not result in transcription of PR. A quantitative comparative analysis demonstrates that inhibiting DNA methyltransferases using 5-aza-2'-deoxycytidine or specific disruption of DNMT1 by small interfering RNAs and treatment with the histone-deacetylase inhibitor Trichostatin A enabled ERa-mediated hormone-dependent expression of endogenous PR. We show that demethylation of a CpG island located in the first exon of PR was a prerequisite for ERa binding to these regulatory sequences. Although not a general requirement, DNA demethylation is also necessary for derepression of a subset of ERa target genes involved in tumorigenesis. PR transcription did not subsist four days after removal of the DNA methyltransferase blocking agents, suggesting that hormone-induced expression of ERa target genes in ERa-negative tumor cells is transient. Our observations support a model where an epigenetic mark confers stable silencing by precluding ERa access to promoters
Vitali, Patrice. « Identification de nouveaux ARN guides de modification et étude fonctionnelle de l'ARN C/D, spécifique du cerveau, MBII-52 ». Toulouse 3, 2005. http://www.theses.fr/2005TOU30032.
Texte intégralHenckel, Amandine. « Relations entre méthylation de l’ADN et modifications des histones au niveau des régions de contrôle de l’empreinte génomique parentale ». Montpellier 2, 2009. http://www.theses.fr/2009MON20130.
Texte intégralResearch on genomic imprinting provides an excellent opportunity to identify the signals that direct epigenetic marks to particular genomic sequences. Genomic imprinting is a form of non-Mendelian inheritance in mammals where some genes are expressed depending on whether they are inherited from the mother or the father. This allele specific expression is regulated by “Imprinting Control Regions” (ICRs), which are marked by allelic histone modifications and DNA methylation. It is not currently known if such allelic chromatin structure exists in germ cell lineages. A key factor to establish DNA methylation in ICRs/germline DMRs is Dnmt3L (De novo methyltransferase 3-Like), through its interaction with a de novo methyltransferase, Dnmt3a. However, the precise mechanism involved in the germline specificity of Dnmt3L targeting is currently unknown. One possibility is that epigenetic modifications other than DNA methylation are already present and are used as a mark to indicate which sequences need to become methylated. In order to identify such a mark, we first explored whether histone modification patterns at ICRs are maintained in absence of DNA methylation imprints in mutant embryos lacking ICR DNA methylation. Secondly, we improved the ChIP technique to look at histone modifications patterns at ICRs of primordial germ cells after the demethylation wave. From these experiments, we showed a functional link between histone modifications and DNA méthylation at ICRs. We also found that some specific histone modifications could be necessary to allow the acquisition of ICR DNA méthylation in male germline
Madugundu, Guru Swamy. « Analysis of radiation induced DNA damage by LC-MS/MS in isolated and cellular DNA ». Thèse, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9465.
Texte intégralRésumé : Les radiations ionisantes induisent une variété de dommages à l'ADN selon des effets directs, correspondant à une oxydation suite à l’éjection d’un électron, et indirecte, médiés par une réaction avec les produits issus de la radiolyse de l’eau environnante, tels que les radicaux hydroxyles (•OH). Au sein d’une cellule, l’importance relative des effets directs et indirects semble être quantitativement similaire en ce qui concerne les dommages induits à l'ADN cellulaire. Nous avons démontré que l'irradiation par rayons Υ-(gamma) de solutions aqueuses d'ADN, dont l’action délétère est principalement véhiculé e par l’intermédiaire des radicaux hydroxyles, peut induire sur l’ADN la formation de toute une palette de modifications. D'autre part, la méthylation et la déméthylation oxydative de la cytosine au sein de couples de dinucléotides CpG jouent un rôle essentiel dans la régulation des gènes. La position C5 de cette cytosine se retrouve fréquemment méthylée par les méthyltransférases (DNMTs) et constitue alors 4-5% de l’ensemble de la cytosine présente au sein de l’ADN. Mon projet de recherche est centralisé autour de l'analyse de la modification des bases de l’ADN suite à leur oxydation dans des composés modèles constitués d'oligonucléotides méthylés et non-méthylés, puis dans l'ADN isolé (extrait de cellules de thymus de veau) et enfin au sein de cultures cellulaires F98 ayant subies une irradiation par rayons Υ-(gamma). De plus, nous avons identifié une série de modifications spécifiques au groupement fonctionnel 2-désoxyribose de l'ADN résultant de l'exposition de l'ADN isolé et cellulaire aux rayonnements ionisants. Nous avons également étudié les conséquences de l’irradiation par des impulsions lasers nanoseconde à 266 nm de cultures cellulaires de lignée humaine (HeLa). Responsable d’une réaction d’oxydation suite à l’éjection d’un électron, l’identification des modifications induites à l’ADN cellulaire suite à l’irradiation laser a permis de mettre en évidence des pontages ADN-ADN caractéristiques entre les bases guanine et thymine (G*-T*). Pour atteindre ces objectifs, nous avons développé plusieurs méthodes d’analyse des modifications de bases au sein de l’ADN isolé et de l'ADN cellulaire basées sur la spectroscopie de masse.
Ajjan, Sophie. « Formes atypiques d'empreinte génomique : transitoire, tissu-spécifique et lignée-spécifique ». Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066251/document.
Texte intégralGenomic imprinting refers to the functional non-equivalence of the two parental genomes in mammals. Imprinted genes are expressed only from the paternal or maternal allele: this mono-allelic expression is regulated by parent-inherited DNA methylation of specific cis-regulatory regions called ICRs (Imprinting Control Regions). There are currently around 120 imprinted genes known in the mouse genome, which are under the control of 20 characterized ICRs, and are generally conserved in Human. My thesis project aimed at characterizing new maternal ICRs and at analyzing their impact on gene regulation, based on a genome-wide methylation screen conducted in the mouse. I participated to revealing the existence of three forms of genomic imprinting, which reflects variable susceptibility to developmentally-regulated DNA methylation changes: 1) ubiquitous and life-long imprinting, which refers to the 20 canonical ICRs, 2) transient, whose existence is limited to preimplantation development, and 3) tissue-specific. More specifically, I deciphered the histone modification profiles of two new maternal ICR associated with the Cdh15 and the Gpr1/Zdbf2 loci and confirmed that the GPR1/ZDBF2 locus is also subject to transient imprinting in Human. My main achievement concerns the characterization of a candidate ICR associated with the Socs5 gene, which I found to be tissue-specific but also strain-specific, pointing towards a new form of imprinting polymorphism. This ICR has an intragenic position and has the characteristics of an enhancer, hypothesis that I am functionally testing in vivo by a CRISPR/Cas9-mediated deletion. The discovery of these new forms of genomic imprinting provides a better understanding of this phenomenon and its impact on phenotypes
Duquesne, Sophie. « Peptides antimicrobiens des entérobactériesEtude de la voie de maturation et du mécanisme d'import de la microcine J25, peptide antimicrobien inhibiteur de l'ARN polymérase ». Phd thesis, Université Pierre et Marie Curie - Paris VI, 2007. http://tel.archives-ouvertes.fr/tel-00193192.
Texte intégralEdmond, Valérie. « Caractérisation de nouvelles fonctions biologiques et modifications post-traductionnelles du facteur d'épissage SC35 dans des modèles cellulaires de carcinomes pulmonaires ». Phd thesis, Grenoble, 2010. http://www.theses.fr/2010GRENV028.
Texte intégralThe protein SC35 belongs to the SR (Ser/Arg-rich) proteins family known to be key regulators of alternative and constitutive splicing. The activity of these proteins is largely controlled by phosphorylation. While some data have provided evidence that expression of SR proteins is deregulated during the carcinogenesis process, little is known about the cellular signaling networks that control SR proteins expression and/or activity in cancer cells. For the first time, we demonstrate that SC35 is an acetylated protein. This post-translational modification involves the acetyltransferase Tip60 and the deacetylase HDAC6. We also provide evidence that phosphorylation/acetylation signaling networks are closely connected to control SC35 expression level and activity. Finally, we demonstrate that these post-translational modifications of SC35 are critical to induce apoptosis in response to genotoxic stresses as well as to trigger senescence in response to sodium butyrate, a histone deacetylase inhibitor, in various human lung carcinoma cell lines. The protein E2F1 is a transcription factor involved in the control of cellular proliferation through its requirement for G1/S phase transition and S phase progression and also for the apoptotic process. In the laboratory, we previously identified the protein SC35 as a new direct transcriptional target of E2F1 and demonstrated that both E2F1 and SC35 proteins cooperate to mediate apoptosis in response to genotoxic stresses. Here, we demonstrate that SC35 also governs the entry and progression into S phase by controlling some E2F1-target genes involved in this setting, such as cyclin E. We provide evidence that the PI3K/AKT signaling pathway is involved in the control of cyclin E expression mediated by both E2F1 and SC35 proteins, notably through the phosphorylation of SC35. We finally describe a direct correlation between cyclin E and P-SC35 protein expression in a series of neuroendocrine lung tumors. Taken together, these results unravel new cellular signaling pathways to control functions of SC35 and open new prospects for the biological consequences of the deregulation of SC35 expression in lung cancer
Edmond, Valérie. « Caractérisation de nouvelles fonctions biologiques et modifications post-traductionnelles du facteur d'épissage SC35 dans des modèles cellulaires de carcinomes pulmonaires ». Phd thesis, Grenoble, 2010. http://tel.archives-ouvertes.fr/tel-00531801.
Texte intégralNoiret, Maud. « Étude des protéines de liaison à l'ARN des familles PTB et ARE-BP au cours du développement chez le xénope ». Phd thesis, Rennes 1, 2012. https://ecm.univ-rennes1.fr/nuxeo/site/esupversions/a420494c-0828-469e-bd2f-60a70118ef9f.
Texte intégralMy work has focused on the function of RNA binding-proteins during early development in Xenopus. I first documented the expression pattern of members of the AU-rich element binding protein (ARE-BP) and of the polypyrimidin tract binding protein (PTB) families during development. Study of the expression patterns of five members of the ARE-BP family (AUF1, KSRP, HuR, TIA1 and TTP) has underlined the broad role and the redundancy of expression of four of these proteins. Conversely, the highly specific expression pattern of TTP in macrophages suggests a potential function for this ARE-BP in hematopoietic development. My study of the PTB family (PTBP1, PTBP2 and PTBP3), has showed that each paralog presents a unique pattern of expression emphasizing their diverse functions during development. From previous work in the lab we knew that morpholino mediated knockdown of both PTBP1 and EXOSC9, a component of the RNA exosome, generated similar defects in the dorsal fin morphology. To identify the molecular origin of these defects we realized the transcriptome analysis by high throughput sequencing (RNA-Seq) of both morphants embryos. I produced cDNA libraries of control and morphant embryos and the sequencing was performed at the Genoscope. Analysis of a known PTBP1 target showed that even modest modifications of alternative splicing could be detected in our data sets. In addition, because these defects are not found in the EXOSC9 morphants it validated its use as an additional screen to exclude splicing events not involved in the epidermal defects. Identification of RNA whose deregulation may be involved in the fin phenotype is currently under study for a set of candidate genes
Bouquet, Sophie-Fanny. « Caractérisation d'une nouvelle voie nucléaire d'adaptation cellulaire à l'hypoxie de la DNA-PK (protéine kinase de l'ADN) ». Toulouse 3, 2008. http://thesesups.ups-tlse.fr/976//.
Texte intégralHypoxia is a frequent microenvironmental stress observed in human tumours. The stress response observed in hypoxic cells results in more aggressive and metastatic cancer phenotypes, associated with resistance to radiation therapy, chemotherapy and poor treatment outcome. A key regulator of the cellular response to oxygen deprivation is the transcription factor, hypoxia-inducible factor-1 (HIF-1) whose function resulting in the induction of a plethora of target genes that collectively confers cellular adaptation to hypoxia. HIF-1 is comprised of a labile alpha sub-unit that is mainly targeted for normoxia-dependent degradation by the proteasomal system whereas its beta sub-unit, HIF-1 beta, or ARNT, is constitutively expressed. We demonstrate here that the DNA dependent protein kinase (DNA-PK) is activated in response to hypoxia in a DNA dependent-manner. We could visualize this activation using phospho-serine 2056 DNA-PKcs and gammaH2AX antibodies. Activation of DNA-PK contributes to the regulation of HIF-1 alpha accumulation and subsequent HIF-1 target gene expression as demonstrated using DNA-PK deficient cells of murine and human origin. Similar decrease in HIF-1 alpha expression was observed in cells deficient in the DNA-PK regulatory sub-unit Ku or in presence of NU7026, a selective inhibitor of the kinase activity of DNA-PK. Furthermore, DNA-PK protects nuclear HIF-1 from proteasomal degradation by the von-Hippel Lindau (VHL) (a component of the E3 ubiquitin ligase complex) pathway. Taken together our results suggest that hypoxia induces DNA modifications and that the acute DNA damage response to hypoxia favours, via the increased expression and function of HIF-1 alpha, the adaptation of cells to this microenvironmental stress
Lin, Xin. « Charaterization of the Phaeodactylum tricornutum epigenome ». Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112235/document.
Texte intégralDNA methylation is the most extensively studied and widely conserved epigenetic mark. Here the first whole genome methylome from a stramenopile, the marine model diatom P. tricornutum is reported. In P. tricornutum, around 6% of the genome was methylated in a mosaic landscape. Extensive methylation in transposable elements (TEs), especially in recently amplified Copia-like elements was found. Over 320 genes were found methylated occurring in three different genomic contexts: in the proximity of TEs, in clusters of methylated genes, and in single genes. Furthermore, genes extensively and completely methylated correlated strongly with transcriptional silencing and differential expression under specific conditions. Finally, it was found that genes likely acquired by horizontal gene transfer from bacteria were preferentially inserted within TE-rich regions, suggesting a mechanism whereby the expression of foreign genes can be buffered following their insertion in the genome. In general, P. tricornutum has low DNA methylation with relatively extensive DNA methylation on TEs and a few methylated genes. This first Stramenopile methylome adds significantly to our understanding of the evolution of DNA methylation in eukaryotes. As for the histone modifications, genome wide distribution of H3K4me2, H3K9me2 and H3K27me3 were examined in P. tricornutum. H3K4me2 is mainly associated with genes while both H3K9me2 and H3K27me3 marks target mainly transposable elements (TEs). The distribution of H3K27me3 is unusual and different from what have been profiled in model species so far. The genes marked by H3K27me3 tend to be lowly and differentially expressed. H3K27me3 and H3K9me2 tend to co-mark not only methylated TEs but also heavily methylated genes, which appears to be important for maintaining the silencing of differentially expressed genes. The combinatorial analysis of different histone marks and DNA methylation gave us an overview of diatom chromatin landscapes, and will help to define conserved structural and functional features
Dabin, Juliette. « Altérations de la chromatine endommagée aux UVC dans les cellules humaines : une histoire d'histones ». Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/Dabin_juliette_complete_2018.pdf.
Texte intégralIn eukaryotic cell nuclei, DNA wrapping around histone proteins in the form of chromatin is a source of epigenetic information that specify gene expression and therefore, cell identity. However, chromatin is also the substrate of all DNA transactions such as transcription, replication and repair. These nuclear processes destabilize the chromatin structure and are thus susceptible to affect the epigenetic information that it carries. During my thesis, I was interested in chromatin dynamics in response to UVC-induced DNA damage in human cells. In particular, I sought to understand how the maintenance of both genome and epigenome integrity are coordinated during DNA repair. To tackle this question, I developed an innovative approach combining local UVC irradiation of human cells and real-time tracking of parental histones, which carry the original epigenetic information. These methods allowed me to characterize parental histone dynamics in UVC-damaged chromatin and to identify the underlying mechanisms. Thus, I show that parental histones are rapidly redistributed around the DNA damage site in a conservative manner, and then recycle within damaged chromatin regions. The major contribution of parental histone to repairing chromatin likely contributes to the epigenome maintenance during DNA damage repair. DNA damage repair is accompanied by new histone incorporation in damaged chromatin regions, which functional relevance is not elucidated yet. To investigate the function of new histone deposition at UVC damage sites, I studied their impact on histone post-translational modifications in damaged chromatin regions. I identified their contribution to a local defect in histone phosphorylations associated with chromosome condensation in early mitosis. This mechanism could serve as a chromatin-based DNA damage checkpoint in early mitosis, which would delay chromosome segregation in response to DNA damage. Altogether, this work put forward the importance of histone dynamics that accompany DNA damage repair in coordinating genome and epigenome maintenance, and open new avenues regarding the role of chromatin plasticity in maintaining cellular homeostasis
El, Khoury Victoria. « Etude de modifications épigénétiques corrélées à l'expression du gène MDR1 et à la texture nucléaire dans des cellules de carcinome pulmonaire H69 sensibles et résistantes à la chimiothérapie ». Reims, 2006. http://www.theses.fr/2006REIMP203.
Texte intégral@Multidrug resistance often results from the expression of P-gp, an efflux pump encoded by the MDR1 gene. However molecular mechanisms that regulate MDR1 gene remain poorly understood. This study examined the consequences of epigenetic modifications on nuclear phenotype and MDR1 gene expression in lung carcinoma cell lines sensitive (H69WT) and resistant to chemotherapy (H69VP). H69VP resistant cells overexpressing MDR1 gene display nuclear texture alterations, as compared with H69WT sensitive cells, underlining a more uniform distribution of chromatin. Treatment with trichostatin A (TSA), a histone deacetylase inhibitor, induces a progressive and transient chromatin decondensation in sensitive and resistant cells respectively. These modifications seem to reflect variations of H3 acetylation levels on the MDR1 promoter. TSA up-regulates MDR1 gene expression in H69WT cells and down-regulates its expression in H69VP cells through a transcription mechanism without affecting MDR1 mRNA stability and independently of MDR1 promoter methylation and PCAF recruitment to the MDR1 inverted CCAAT box. Translation inhibition reduces these modulations without suppressing them, suggesting that TSA modifies the expression and DNA binding of transcription factors implicated in the regulation of MDR1 gene. These findings indicate that HDAC inhibitors may represent potential anticancer drugs in multidrug resistant tumors
Broucqsault, Natacha. « Régulation épigénétique du locus subtélomérique 4q35 et contribution du macrosatellite D4Z4 dans la dystrophie facio-scapulo-humérale ». Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5099.
Texte intégralHird more frequently myopathy, the facioscapulohumeral dystrophy is an enigmatic disease. It is associated with the macrosatellite D4Z4 contraction since 90’s but the origin of the modifications observable in patients remains unclear. That’s why, we have focused our work in different aspects of this disease. First of all, we have studied expression of 4q35 and muscular genes in fetuses and adults carrying a contraction of the D4Z4 macrosatellite and shown that the molecular deregulations can be observed since the fetal stage. So, we have validated this model as an interesting model to study the early FSHD pathogenesis. Secondly, we have been interested in epigenetic regulation of two genes located in the 4q35 region and have observed a modulation of their expression in a global epigenetic modulation contest. Those deregulations depend on the number of D4Z4 repeats. Finally, we have analyzed the region regulation by telomere position effect and have noted only some genes are deregulated by this epigenetic mechanism. With those results, we have progressed in the FSHD pathogenesis knowledge and we have validated a new model to study this pathology
Noiret, Maud. « Étude des protéines de liaison à l'ARN des familles PTB et ARE-BP au cours du développement chez le xénope ». Phd thesis, Université Rennes 1, 2012. http://tel.archives-ouvertes.fr/tel-00786151.
Texte intégral