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Méthylation de l'ADN : fonctions et ciblage au cours du développement chez la souris

Abstract : Cytosine methylation is an epigenetic modification catalyzed by the family of DNA methyltransferases (DNMTs). This modification is involved in gene repression when it is addressed to CpG islands in gene promoters. Global DNA methylation reprogramming occurs in mice during the early phases of embryogenesis, which is critical for proper embryo development. However, the contribution of different DNMTs in genome methylation and the mechanisms that target DNA methylation to specific genes during embryonic development are poorly understood. By combining genomic mapping with genetically modified mouse lines, my Thesis work clarified the contribution of the different DNMTs in genome methylation in the embryo: DNMT3A and DNMT3B are strictly involved in de novo methylation, and DNMT1 is strictly involved in the maintenance of DNA methylation during cellular divisions. In addition, the analysis of globally demethylated embryos revealed numerous functions of DNA methylation in maintaining the transcriptomic intergrity of the embryo by repressing germline genes, developmental genes, cryptic promoters as well as a large panel of transposons.
 In the second part of my Thesis, I studied the role of the E2F6 transcription factor in the targeting of DNA methylation in vivo in mice. My results demonstrate that E2F6 facilitates the acquisition of DNA methylation in the promoters of germline genes and is required to initiate their long-term epigenetic silencing during embryogenesis. Collectively, this work contributes to a better understanding of the functions and targeting mechanisms of DNA methylation during mammalian embryogenesis.
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Submitted on : Tuesday, January 4, 2022 - 2:20:13 PM
Last modification on : Sunday, June 26, 2022 - 3:30:36 AM


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  • HAL Id : tel-03510184, version 1



Thomas Dahlet. Méthylation de l'ADN : fonctions et ciblage au cours du développement chez la souris. Génomique, Transcriptomique et Protéomique [q-bio.GN]. Université de Strasbourg, 2019. Français. ⟨NNT : 2019STRAJ075⟩. ⟨tel-03510184⟩



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