학술논문
XIST dampens X chromosome activity in a SPEN-dependent manner during early human development.
Document Type
Academic Journal
Author
Alfeghaly C; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Castel G; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Cazottes E; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Moscatelli M; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Moinard E; Center for Research in Transplantation and Translational Immunology (CR2TI), CHU Nantes, Inserm, Nantes Université, Nantes, France.; Casanova M; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Boni J; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Mahadik K; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Lammers J; Service de Biologie de la Reproduction, CHU Nantes, Nantes Université, Nantes, France.; Freour T; Service de Biologie de la Reproduction, CHU Nantes, Nantes Université, Nantes, France.; Chauviere L; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Piqueras C; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Boers R; Department of Developmental Biology, Erasmus University Medical Center, Rotterdam, Netherlands.; Boers J; Department of Developmental Biology, Erasmus University Medical Center, Rotterdam, Netherlands.; Gribnau J; Department of Developmental Biology, Erasmus University Medical Center, Rotterdam, Netherlands.; David L; Center for Research in Transplantation and Translational Immunology (CR2TI), CHU Nantes, Inserm, Nantes Université, Nantes, France.; BioCore, CNRS, CHU Nantes, Inserm, Nantes Université, Nantes, France.; Ouimette JF; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France.; Rougeulle C; Epigenetics and Cell Fate, CNRS, Université Paris Cité, Paris, France. claire.rougeulle@u-paris.fr.
Source
Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101186374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-9985 (Electronic) Linking ISSN: 15459985 NLM ISO Abbreviation: Nat Struct Mol Biol Subsets: MEDLINE
Subject
Language
English
Abstract
XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female preimplantation embryos without triggering X chromosome silencing. The XACT (X-active coating transcript) lncRNA coaccumulates with XIST on active X chromosomes and may antagonize XIST function. Here, we used human embryonic stem cells in a naive state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during preimplantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and dampens the transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional before XCI, confirms the existence of a transient process of X chromosome dosage compensation and reveals that XCI and dampening rely on the same set of factors.
(© 2024. The Author(s).)
(© 2024. The Author(s).)