HIRA stabilizes skeletal muscle lineage identity.
Acetylation
Animals
Cell Cycle Proteins
/ deficiency
Cell Line
Cell Lineage
/ genetics
Genetic Loci
Histone Chaperones
/ deficiency
Histones
/ metabolism
Lysine
/ metabolism
Mice
Muscle Development
/ genetics
Muscle, Skeletal
/ injuries
Regeneration
Regulatory Sequences, Nucleic Acid
/ genetics
Satellite Cells, Skeletal Muscle
/ metabolism
Transcription Factors
/ deficiency
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 06 2021
08 06 2021
Historique:
received:
21
10
2020
accepted:
17
05
2021
entrez:
9
6
2021
pubmed:
10
6
2021
medline:
16
6
2021
Statut:
epublish
Résumé
The epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates remain poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications, consistent with a role in maintaining skeletal muscle cellular identity. We demonstrate that conditional ablation of HIRA in muscle stem cells of adult mice compromises their capacity to regenerate and self-renew, leading to tissue repair failure. Chromatin analysis of Hira-deficient cells show a significant reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. Additionally, we find that genes from alternative lineages are ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, we conclude that HIRA sustains the chromatin landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.
Identifiants
pubmed: 34103504
doi: 10.1038/s41467-021-23775-9
pii: 10.1038/s41467-021-23775-9
pmc: PMC8187366
doi:
Substances chimiques
Cell Cycle Proteins
0
Hira protein, mouse
0
Histone Chaperones
0
Histones
0
Transcription Factors
0
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3450Références
Genes Dev. 2010 Jun 15;24(12):1253-65
pubmed: 20504901
Nat Commun. 2019 Sep 18;10(1):4256
pubmed: 31534153
J Biophys Biochem Cytol. 1961 Feb;9:493-5
pubmed: 13768451
Bioinformatics. 2010 Jul 15;26(14):1783-5
pubmed: 20562416
Cell Stem Cell. 2009 Jun 5;4(6):535-47
pubmed: 19497282
Nat Methods. 2017 Oct;14(10):959-962
pubmed: 28846090
PLoS Genet. 2010 Apr 01;6(4):e1000897
pubmed: 20368965
Cell Cycle. 2008 May 1;7(9):1173-7
pubmed: 18418041
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5
pubmed: 27079975
Bioinformatics. 2016 Jul 15;32(14):2089-95
pubmed: 27153568
Dev Biol. 2018 Jan 15;433(2):200-209
pubmed: 28811217
Cell. 2013 Jul 18;154(2):452-64
pubmed: 23870131
Nat Biotechnol. 2015 May;33(5):543-8
pubmed: 25803306
Nat Biotechnol. 2016 Feb;34(2):184-191
pubmed: 26780180
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nucleic Acids Res. 2016 Jul 8;44(W1):W3-W10
pubmed: 27137889
Nat Genet. 2019 Jun;51(6):941-946
pubmed: 31152160
Curr Opin Cell Biol. 2008 Jun;20(3):341-8
pubmed: 18508253
Development. 2011 Sep;138(17):3625-37
pubmed: 21828091
Nat Protoc. 2008;3(3):398-409
pubmed: 18323811
Nat Methods. 2013 Dec;10(12):1213-8
pubmed: 24097267
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Bioinformatics. 2015 Jul 15;31(14):2382-3
pubmed: 25765347
Nat Cell Biol. 2008 Jan;10(1):102-9
pubmed: 18066050
Neuron. 2012 Apr 12;74(1):122-35
pubmed: 22500635
Epigenetics Chromatin. 2015 Jan 15;8(1):4
pubmed: 25621013
Nature. 2009 May 7;459(7243):108-12
pubmed: 19295514
Proc Natl Acad Sci U S A. 2011 May 31;108(22):E149-58
pubmed: 21551099
EMBO J. 2012 Jun 29;31(13):2994-3007
pubmed: 22569126
Science. 2007 Aug 24;317(5841):1087-90
pubmed: 17717186
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Cell Rep. 2013 Jul 11;4(1):189-204
pubmed: 23810552
Development. 1995 Mar;121(3):637-49
pubmed: 7720572
Trends Genet. 2020 Feb;36(2):118-131
pubmed: 31818514
Cell Rep. 2016 Jan 5;14(1):103-114
pubmed: 26725110
Genes Dev. 2008 Jul 1;22(13):1828-37
pubmed: 18593883
Annu Rev Cell Dev Biol. 2007;23:645-73
pubmed: 17506689
PLoS One. 2016 Jan 25;11(1):e0147198
pubmed: 26807982
Genes Dev. 2010 Jul 1;24(13):1334-8
pubmed: 20595228
Cell. 2010 Mar 5;140(5):678-91
pubmed: 20211137
Cell Rep. 2017 Nov 14;21(7):1982-1993
pubmed: 29141227
J Mol Biol. 2017 Jun 30;429(13):1924-1933
pubmed: 27871933
Cell. 2007 Jun 1;129(5):999-1010
pubmed: 17540178
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Cancer Genet. 2011 May;204(5):252-9
pubmed: 21665178
Genes Dev. 2002 Jan 1;16(1):6-21
pubmed: 11782440
Nucleic Acids Res. 2015 Jan;43(2):775-86
pubmed: 25539924
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):85-90
pubmed: 21173268
Nucleic Acids Res. 2017 Sep 6;45(15):8758-8772
pubmed: 28549158
Nature. 2006 Aug 3;442(7102):568-71
pubmed: 16760928