Study of the Xist transcriptional network
type: Distribution
access URL: https://theses.hal.science/tel-00815096
format: HTML
issued: 2026-05-11T10:25:14.883307
modified: 2026-05-11T10:25:14.811125

test_moissonnage_selune
type: Agent

Study of the Xist transcriptional network
type: Dataset
contact point: Organization
  fn: CCSD
keyword: structure-tridimensionnelle
keyword: epigenetics
keyword: non-coding-rna
keyword: threedimensional-structure
keyword: sdvgenghlife-sciences-q-biogeneticshuman-genetics
keyword: transcriptional-regulation
keyword: x-chromosome-inactivation
keyword: inactivation-du-chromosome-x
keyword: theses
keyword: regulation-transcriptionnelle
keyword: infoeu-reposemanticsdoctoralthesis
keyword: epigenetique
keyword: arn-non-codant
landing page: https://theses.hal.science/tel-00815096
description: X-chromosome inactivation is evolution's answer to compensate for the gonosomal discrepancy between male (XY) and female (XX). This phenomenon therefore serves to put both sexes on an equal footing by limiting the amount of transcripts produced from the X chromosomes in female cells. During my Ph.D., I tried to contribute to the study of transcriptional regulatory mechanisms, including activation of the two main players in inactivation: Xist (for X-inactive Specific transcript) and Tsix, its antisense transcript. Both genes produce non-coding transcripts essential for correct initiation of this epigenetic phenomenon. Xist RNA coats one of the two X chromosomes in female cells to induce inactivation, and does so in a manner very related to the early embryo development. During these four years, I began to map the binding of several proteins along the Xist/Tsix locus in order to obtain a better understanding of the mechanisms leading to Xist overexpression following the disappearance of its repressors during differentiation. This mapping has been performed in several wild-type or mutant mouse embryonic stem cell strains (which are capable of summarizing XCI ex vivo). I was able to establish a model for transcriptional regulation of the non-coding Xist RNA, involving several proteins known for their role in transcriptional regulation (CTCF and YY1) as well as in the formation of three-dimensional structures (cohesin). The relevance of this model is reinforced by our studies showing that many aspects of this model are conserved throughout evolution (including humans). I have also contributed to the discovery of new Tsix activators, some pluripotency factors binding to the DxPas34 minisatellite to regulate the antisense's transcription elongation. These results thus provide important information about the mechanisms regulating Xchromosome inactivation during early development of the embryo.
identifier: NNT: 2010PA066319
issued: 2026-05-11T10:25:14.878886
language: fr
modified: 2026-05-11T10:25:14.878892