GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of long-range enhancers.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
01
07
2022
accepted:
22
09
2023
medline:
13
11
2023
pubmed:
7
11
2023
entrez:
6
11
2023
Statut:
ppublish
Résumé
X-chromosome inactivation (XCI) balances gene expression between the sexes in female mammals. Shortly after fertilization, upregulation of Xist RNA from one X chromosome initiates XCI, leading to chromosome-wide gene silencing. XCI is maintained in all cell types, except the germ line and the pluripotent state where XCI is reversed. The mechanisms triggering Xist upregulation have remained elusive. Here we identify GATA transcription factors as potent activators of Xist. Through a pooled CRISPR activation screen in murine embryonic stem cells, we demonstrate that GATA1, as well as other GATA transcription factors can drive ectopic Xist expression. Moreover, we describe GATA-responsive regulatory elements in the Xist locus bound by different GATA factors. Finally, we show that GATA factors are essential for XCI induction in mouse preimplantation embryos. Deletion of GATA1/4/6 or GATA-responsive Xist enhancers in mouse zygotes effectively prevents Xist upregulation. We propose that the activity or complete absence of various GATA family members controls initial Xist upregulation, XCI maintenance in extra-embryonic lineages and XCI reversal in the epiblast.
Identifiants
pubmed: 37932452
doi: 10.1038/s41556-023-01266-x
pii: 10.1038/s41556-023-01266-x
pmc: PMC10635832
doi:
Substances chimiques
GATA Transcription Factors
0
RNA, Long Noncoding
0
XIST non-coding RNA
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1704-1715Informations de copyright
© 2023. The Author(s).
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