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Deciphering X chromosome architecture during mouse preimplantation development

Abstract : 3D folding of the genome is thought to play an important role in gene regulation. Recently, a new era in our understanding of genome organization has been opened up thanks to the plethora of new techniques enabling interactions between loci to be captured and sequenced in depth. Several layers of chromosome organization have been identified. In particular topologically associating domains (TADs) have been uncovered as a level of folding at the megabase scale. TADs represent preferential cis-interactions within domains across chromosomes and are thought to sometimes operate as regulatory units in coordinating gene expression. Although TADs are largely constant during cellular differentiation and are conserved between man and mouse, drastic changes in conformation can occur in some biological processes such as X-chromosome inactivation (XCI). XCI achieves dosage compensation in mammalian females, be rendering one X chromosome silent. The conformation of the inactive X is strikingly different from its active counterpart: with a global loss of local structure and formation of two large domains. The aim of my PhD was to explore genome architecture - and more specifically X-chromosome structure after fertilization - when the newly formed embryo reprograms its chromatin toward totipotency, and activates its own genome. In mouse, this structural and functional reorganization coincides with the onset of imprinted XCI in female embryos. Using two complementary techniques, 3D DNA FISH with super resolution microscopy and allele-specific, single-cell HiC, I examined the dynamics of genome reorganization in mouse pre-implantation embryos during and after genome activation. I also characterized the structural changes of the paternal X chromosome while it is inactivated. This study describes the conformation dynamics of the genome in the early embryo and in particular of the X chromosome as it undergoes XCI, thus contributing to our understanding o f the intricate interplay between structure and function at the onset of development.
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Submitted on : Wednesday, May 11, 2022 - 4:24:19 PM
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  • HAL Id : tel-03665345, version 1

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Noémie Ranisavljevic. Deciphering X chromosome architecture during mouse preimplantation development. Development Biology. Université Paris Saclay (COmUE), 2017. English. ⟨NNT : 2017SACLS546⟩. ⟨tel-03665345⟩

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