JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation.
CP: Molecular biology
cell differentiation
chromatin
decidualization
embryonic stem cell
endometrial stromal sarcoma
endometrium
epigenetics
histone acetylation
histone modification
polycomb
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
31 05 2022
31 05 2022
Historique:
received:
09
04
2021
revised:
04
03
2022
accepted:
06
05
2022
entrez:
1
6
2022
pubmed:
2
6
2022
medline:
7
6
2022
Statut:
ppublish
Résumé
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis.
Identifiants
pubmed: 35649353
pii: S2211-1247(22)00664-7
doi: 10.1016/j.celrep.2022.110889
pmc: PMC9637993
pii:
doi:
Substances chimiques
Co-Repressor Proteins
0
DNA-Binding Proteins
0
Histones
0
JAZF1 protein, human
0
Neoplasm Proteins
0
SUZ12 protein, human
0
Transcription Factors
0
Polycomb Repressive Complex 2
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110889Subventions
Organisme : Wellcome Trust
ID : 212233/Z/18/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C416/A18088
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Nat Commun. 2021 Jul 28;12(1):4592
pubmed: 34321472
Endocr Rev. 2014 Dec;35(6):851-905
pubmed: 25141152
Mol Cell. 2015 Mar 5;57(5):769-783
pubmed: 25620564
Cell Rep. 2016 Oct 4;17(2):583-595
pubmed: 27705803
Br J Cancer. 2007 Nov 5;97(9):1194-9
pubmed: 17895898
Nat Struct Mol Biol. 2016 Jul;23(7):682-690
pubmed: 27294783
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Mol Cell Biol. 2007 May;27(10):3769-79
pubmed: 17339329
Mol Cell. 2012 Dec 14;48(5):723-33
pubmed: 23122415
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Mol Hum Reprod. 2017 Sep 1;23(9):646-653
pubmed: 28911214
Genes Chromosomes Cancer. 2016 Nov;55(11):834-46
pubmed: 27219024
Genes Dev. 2010 Feb 15;24(4):368-80
pubmed: 20123894
Genome Res. 2016 Jul;26(7):896-907
pubmed: 27197219
Epigenomics. 2018 Sep;10(9):1243-1257
pubmed: 30212243
Int J Cancer. 2014 Mar 1;134(5):1112-22
pubmed: 23959973
Elife. 2021 Sep 06;10:
pubmed: 34487490
Nature. 2012 Jan 04;481(7381):389-93
pubmed: 22217937
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20001-6
pubmed: 18077430
Gynecol Oncol. 2012 Apr;125(1):141-4
pubmed: 22119993
Dev Biol. 2015 Jun 15;402(2):291-305
pubmed: 25912690
Mol Cell. 2016 Nov 17;64(4):659-672
pubmed: 27863226
Nat Protoc. 2012 Sep;7(9):1728-40
pubmed: 22936215
Cell Rep. 2020 Jul 7;32(1):107846
pubmed: 32640216
Oncotarget. 2017 Jan 17;8(3):4062-4078
pubmed: 27845897
Genes Chromosomes Cancer. 2020 Jul;59(7):428-432
pubmed: 32237188
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell. 2009 Dec 24;139(7):1303-14
pubmed: 20064376
Mol Cell. 2021 Feb 4;81(3):488-501.e9
pubmed: 33338397
Bioinformatics. 2019 Jun 1;35(12):2084-2092
pubmed: 30395178
Virchows Arch. 2019 Oct;475(4):527-531
pubmed: 31101969
Cell. 2006 Apr 21;125(2):301-13
pubmed: 16630818
Genes Dev. 2006 May 1;20(9):1123-36
pubmed: 16618801
Nat Cell Biol. 2006 May;8(5):532-8
pubmed: 16570078
Nature. 2011 Jan 20;469(7330):343-9
pubmed: 21248841
Nat Biotechnol. 2020 Mar;38(3):276-278
pubmed: 32055031
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198
pubmed: 31066453
Mol Cell. 2019 Nov 7;76(3):423-436.e3
pubmed: 31521506
Cell Stem Cell. 2010 Feb 5;6(2):153-66
pubmed: 20144788
J Clin Invest. 2018 Jan 2;128(1):233-247
pubmed: 29202469
Gynecol Oncol. 2018 May;149(2):388-393
pubmed: 29544705
Mol Cell. 2016 Jan 7;61(1):27-38
pubmed: 26669263
Nature. 2020 Jul;583(7814):127-132
pubmed: 32555459
Cancer Res. 2006 Jan 1;66(1):107-12
pubmed: 16397222
Nat Struct Mol Biol. 2017 Dec;24(12):1028-1038
pubmed: 29058709
Mol Cell. 2019 Jun 6;74(5):1020-1036.e8
pubmed: 31029541
Stem Cells. 2011 Feb;29(2):229-40
pubmed: 21732481
Mol Cell. 2019 Nov 7;76(3):437-452.e6
pubmed: 31521505
Biol Reprod. 2013 Mar 28;88(3):80
pubmed: 23349235
PLoS One. 2012;7(6):e39354
pubmed: 22761769
Mol Endocrinol. 2011 Nov;25(11):1892-903
pubmed: 21903722
Am J Surg Pathol. 2011 Sep;35(9):1364-72
pubmed: 21836477
Nat Struct Mol Biol. 2012 Dec;19(12):1273-81
pubmed: 23160351
Nat Genet. 2021 Dec;53(12):1698-1711
pubmed: 34857954
Development. 2016 Aug 1;143(15):2716-23
pubmed: 27317809
BMC Genomics. 2009 Jan 14;10:22
pubmed: 19144180
Nat Struct Mol Biol. 2018 Mar;25(3):225-232
pubmed: 29483650
Nucleic Acids Res. 2004 Aug 09;32(14):4194-204
pubmed: 15302918
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Mol Cell. 2018 Mar 1;69(5):840-852.e5
pubmed: 29499137
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Elife. 2017 Dec 11;6:
pubmed: 29227245
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6348-53
pubmed: 11371647
Mol Cell. 2018 May 3;70(3):408-421.e8
pubmed: 29628311
Nat Cell Biol. 2011 Aug 21;13(9):1051-61
pubmed: 21857669
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Expert Rev Mol Diagn. 2017 May;17(5):515-522
pubmed: 28335657
Nature. 2017 Sep 14;549(7671):287-291
pubmed: 28869966
Genes Dev. 2007 Aug 1;21(15):1869-81
pubmed: 17671089
Sci Rep. 2019 Jun 27;9(1):9354
pubmed: 31249361
Nature. 1987 Mar 19-25;326(6110):292-5
pubmed: 3821905
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
Sci Adv. 2019 Jul 03;5(7):eaax2887
pubmed: 31281901
Mol Cell. 2016 Nov 17;64(4):645-658
pubmed: 27863225
Int J Mol Sci. 2021 Jan 12;22(2):
pubmed: 33445503
Nature. 2006 May 18;441(7091):349-53
pubmed: 16625203
Nat Genet. 2018 Jul;50(7):1002-1010
pubmed: 29808031
Nat Cell Biol. 2010 Jun;12(6):618-24
pubmed: 20473294
Bioinformatics. 2017 Sep 15;33(18):2938-2940
pubmed: 28645171
Genes Dev. 2002 Apr 1;16(7):784-9
pubmed: 11937486
Cell Rep. 2022 Feb 1;38(5):110329
pubmed: 35108527
Cancer Genet Cytogenet. 2008 Sep;185(2):74-7
pubmed: 18722875
Science. 2018 Feb 23;359(6378):940-944
pubmed: 29348366
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Mol Cell. 2018 Jun 21;70(6):1149-1162.e5
pubmed: 29932905
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2488-93
pubmed: 24550272
Genes Dev. 2018 Jun 1;32(11-12):794-805
pubmed: 29891558
EMBO J. 2004 Oct 13;23(20):4061-71
pubmed: 15385962
Cell Rep. 2014 Nov 6;9(3):1163-70
pubmed: 25437568
PLoS Genet. 2012;8(3):e1002576
pubmed: 22438827