The role of Xist-mediated Polycomb recruitment in the initiation of X-chromosome inactivation.
Animals
Female
Histones
/ metabolism
Lysine
/ metabolism
Methylation
Mice
Models, Genetic
Mutation
/ genetics
Polycomb-Group Proteins
/ metabolism
Protein Interaction Maps
RNA, Long Noncoding
/ metabolism
Repetitive Sequences, Nucleic Acid
/ genetics
Transcription, Genetic
X Chromosome
/ genetics
X Chromosome Inactivation
/ genetics
Xist
PRC1
PRC2
X-chromosome inactivation
chromatin
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
04 10 2019
04 10 2019
Historique:
received:
28
02
2019
revised:
29
07
2019
accepted:
06
08
2019
pubmed:
29
8
2019
medline:
12
5
2020
entrez:
29
8
2019
Statut:
ppublish
Résumé
Xist RNA has been established as the master regulator of X-chromosome inactivation (XCI) in female eutherian mammals, but its mechanism of action remains unclear. By creating novel Xist-inducible mutants at the endogenous locus in male mouse embryonic stem (ES) cells, we dissect the role of the conserved A-B-C-F repeats in the initiation of XCI. We find that transcriptional silencing can be largely uncoupled from Polycomb repressive complex 1 and complex 2 (PRC1/2) recruitment, which requires B and C repeats. Xist ΔB+C RNA specifically loses interaction with PCGF3/5 subunits of PRC1, while binding of other Xist partners is largely unaffected. However, a slight relaxation of transcriptional silencing in Xist ΔB+C indicates a role for PRC1/2 proteins in early stabilization of gene repression. Distinct modules within the Xist RNA are therefore involved in the convergence of independent chromatin modification and gene repression pathways. In this context, Polycomb recruitment seems to be of moderate relevance in the initiation of silencing.
Identifiants
pubmed: 31456285
doi: 10.15252/embr.201948019
pmc: PMC6776897
doi:
Substances chimiques
Histones
0
Polycomb-Group Proteins
0
RNA, Long Noncoding
0
XIST non-coding RNA
0
Lysine
K3Z4F929H6
Banques de données
GEO
['GSE123743']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e48019Subventions
Organisme : MEC|Fundação para a Ciência e a Tecnologia (FCT)
ID : PTDC/BIA-MOL/29320/2017
Pays : International
Organisme : MEC|Fundação para a Ciência e a Tecnologia (FCT)
ID : UID/BIM/50005/2019
Pays : International
Organisme : Wellcome Trust
ID : 201369/Z/16/Z
Pays : United Kingdom
Organisme : EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)
ID : ERC-ADG-2014 671027
Pays : International
Organisme : National Institute for Health Research (NIHR)
ID : NIH P50-HG007735
Pays : International
Organisme : Scleroderma Research Foundation (SRF)
Pays : International
Organisme : MEC|Fundação para a Ciência e a Tecnologia (FCT)
ID : PTDC/BEX-BCM/2612/2014
Pays : International
Organisme : MEC|Fundação para a Ciência e a Tecnologia (FCT)
ID : IF/00242/2014
Pays : International
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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