Xist exerts gene-specific silencing during XCI maintenance and impacts lineage-specific cell differentiation and proliferation during hematopoiesis.

Journal Article (Journal Article)

X chromosome inactivation (XCI) is a dosage compensation phenomenon that occurs in females. Initiation of XCI depends on Xist RNA, which triggers silencing of one of the two X chromosomes, except for XCI escape genes that continue to be biallelically expressed. In the soma XCI is stably maintained with continuous Xist expression. How Xist impacts XCI maintenance remains an open question. Here we conditionally delete Xist in hematopoietic system of mice and report differentiation and cell cycle defects in female hematopoietic stem and progenitor cells (HSPCs). By utilizing female HSPCs and mouse embryonic fibroblasts, we find that X-linked genes show variable tolerance to Xist loss. Specifically, XCI escape genes exhibit preferential transcriptional upregulation, which associates with low H3K27me3 occupancy and high chromatin accessibility that accommodates preexisting binding of transcription factors such as Yin Yang 1 (YY1) at the basal state. We conclude that Xist is necessary for gene-specific silencing during XCI maintenance and impacts lineage-specific cell differentiation and proliferation during hematopoiesis.

Full Text

Duke Authors

Cited Authors

  • Yang, T; Ou, J; Yildirim, E

Published Date

  • August 1, 2022

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 4464 -

PubMed ID

  • 35915095

Pubmed Central ID

  • PMC9343370

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-022-32273-5

Language

  • eng

Conference Location

  • England