Distinct roles for CKM-Mediator in controlling Polycomb-dependent chromosomal interactions and priming genes for induction.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
12
11
2021
accepted:
22
08
2022
pubmed:
12
10
2022
medline:
19
10
2022
entrez:
11
10
2022
Statut:
ppublish
Résumé
Precise control of gene expression underpins normal development. This relies on mechanisms that enable communication between gene promoters and other regulatory elements. In embryonic stem cells (ESCs), the cyclin-dependent kinase module Mediator complex (CKM-Mediator) has been reported to physically link gene regulatory elements to enable gene expression and also prime genes for induction during differentiation. Here, we show that CKM-Mediator contributes little to three-dimensional genome organization in ESCs, but it has a specific and essential role in controlling interactions between inactive gene regulatory elements bound by Polycomb repressive complexes (PRCs). These interactions are established by the canonical PRC1 (cPRC1) complex but rely on CKM-Mediator, which facilitates binding of cPRC1 to its target sites. Importantly, through separation-of-function experiments, we reveal that this collaboration between CKM-Mediator and cPRC1 in creating long-range interactions does not function to prime genes for induction during differentiation. Instead, we discover that priming relies on an interaction-independent mechanism whereby the CKM supports core Mediator engagement with gene promoters during differentiation to enable gene activation.
Identifiants
pubmed: 36220895
doi: 10.1038/s41594-022-00840-5
pii: 10.1038/s41594-022-00840-5
pmc: PMC9568430
doi:
Substances chimiques
Mediator Complex
0
Polycomb-Group Proteins
0
Polycomb Repressive Complex 1
EC 2.3.2.27
Cyclin-Dependent Kinases
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1000-1010Subventions
Organisme : Wellcome Trust
ID : 209400/Z/17/Z
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Nat Rev Mol Cell Biol. 2018 Apr;19(4):262-274
pubmed: 29209056
Cell. 2017 Oct 5;171(2):305-320.e24
pubmed: 28985562
Mol Cell Biol. 2005 Aug;25(15):6694-706
pubmed: 16024804
Cell. 2017 Oct 19;171(3):557-572.e24
pubmed: 29053968
Nucleic Acids Res. 2020 Apr 6;48(6):2942-2955
pubmed: 31996894
Elife. 2019 May 24;8:
pubmed: 31124784
Transcription. 2019 Apr;10(2):76-90
pubmed: 30585107
Nature. 2013 Oct 24;502(7472):499-506
pubmed: 24153303
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4672-7
pubmed: 25825760
J Biol Chem. 2021 Jan-Jun;296:100734
pubmed: 33933450
Genome Biol. 2016 Jun 15;17(1):127
pubmed: 27306882
Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5
pubmed: 27079975
Mol Cell. 2016 Feb 4;61(3):461-473
pubmed: 26833089
Genes Dev. 2021 May 1;35(9-10):749-770
pubmed: 33888563
J Pathol. 2015 Dec;237(4):508-19
pubmed: 26235356
Cell Stem Cell. 2013 Nov 7;13(5):602-16
pubmed: 24035354
Mol Cell. 2019 Jun 6;74(5):1037-1052.e7
pubmed: 31029542
Crit Rev Biochem Mol Biol. 2013 Nov-Dec;48(6):575-608
pubmed: 24088064
Nature. 2010 Sep 23;467(7314):430-5
pubmed: 20720539
Cell Rep. 2019 Nov 12;29(7):1974-1985.e6
pubmed: 31722211
Science. 2002 Nov 1;298(5595):1039-43
pubmed: 12351676
Genes Dev. 2021 Aug 1;35(15-16):1175-1189
pubmed: 34301767
Sci Adv. 2020 Jan 10;6(2):eaax4001
pubmed: 31950077
Dev Cell. 2014 Jan 13;28(1):94-101
pubmed: 24374176
Genome Biol. 2014;15(12):550
pubmed: 25516281
Development. 2010 Aug;137(16):2723-31
pubmed: 20630950
J Biochem. 2015 Nov;158(5):373-84
pubmed: 26002960
Mol Cell Biol. 2009 Feb;29(3):650-61
pubmed: 19047373
Nat Genet. 2020 Jul;52(7):719-727
pubmed: 32483291
Nat Genet. 2021 Jul;53(7):1036-1049
pubmed: 34183853
NAR Genom Bioinform. 2021 May 22;3(2):lqab040
pubmed: 34046591
Biotechniques. 2017 Feb 1;62(2):53-61
pubmed: 28193148
Cell Stem Cell. 2015 Dec 3;17(6):748-757
pubmed: 26637943
Cell. 2017 May 4;169(4):693-707.e14
pubmed: 28475897
Development. 2001 May;128(9):1587-97
pubmed: 11290297
Science. 2018 Jul 27;361(6400):412-415
pubmed: 29930094
Development. 2020 Jun 11;147(11):
pubmed: 32439758
Nat Commun. 2021 Jan 22;12(1):531
pubmed: 33483495
Nat Commun. 2021 Sep 9;12(1):5341
pubmed: 34504070
Cell. 2014 Jun 5;157(6):1445-1459
pubmed: 24856970
Biol Reprod. 2018 Apr 1;98(4):449-464
pubmed: 29325037
Nat Commun. 2020 Jun 3;11(1):2798
pubmed: 32493925
Genes Dev. 2020 Jul 1;34(13-14):931-949
pubmed: 32439634
Cell. 2011 Jan 21;144(2):214-26
pubmed: 21241892
Mol Cell. 2010 May 14;38(3):452-64
pubmed: 20471950
Nat Commun. 2016 Jan 13;7:10291
pubmed: 26759081
Cell. 2017 May 18;169(5):930-944.e22
pubmed: 28525758
Mol Cell Biol. 2007 Sep;27(17):6177-82
pubmed: 17620419
Elife. 2018 May 29;7:
pubmed: 29809150
Mol Cell. 2019 Jun 6;74(5):1020-1036.e8
pubmed: 31029541
Mol Cell. 2019 Nov 7;76(3):485-499.e8
pubmed: 31495563
Cell. 2013 Jun 6;153(6):1281-95
pubmed: 23706625
Genes Dev. 2011 Oct 15;25(20):2210-21
pubmed: 22012622
Mol Cell. 2018 Jul 5;71(1):73-88.e5
pubmed: 30008320
Science. 2004 Nov 26;306(5701):1574-7
pubmed: 15567868
Nature. 2014 Aug 7;512(7512):96-100
pubmed: 25043061
Mol Cell. 2005 Apr 1;18(1):83-96
pubmed: 15808511
Nature. 2011 Feb 10;470(7333):279-83
pubmed: 21160473
Nat Genet. 2015 Oct;47(10):1179-1186
pubmed: 26323060
Nat Genet. 2021 Apr;53(4):487-499
pubmed: 33795866
Curr Opin Genet Dev. 2020 Apr;61:1-8
pubmed: 32199341
Science. 2018 Sep 28;361(6409):1341-1345
pubmed: 30262496
Cell. 2017 Apr 6;169(2):216-228.e19
pubmed: 28388407
Mol Cell. 2007 Jul 6;27(1):121-33
pubmed: 17612495
Cell. 2019 Aug 22;178(5):1145-1158.e20
pubmed: 31402173
Genes Dev. 2003 Aug 1;17(15):1823-8
pubmed: 12897052
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Transcription. 2010 Jul-Aug;1(1):4-12
pubmed: 21327159
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Mol Cell. 2019 Nov 7;76(3):473-484.e7
pubmed: 31494034
Nat Commun. 2021 Jul 16;12(1):4344
pubmed: 34272393
Science. 2017 Mar 10;355(6329):1081-1084
pubmed: 28280206
Nat Rev Genet. 2018 Dec;19(12):789-800
pubmed: 30367165
Genes Dev. 2009 Feb 15;23(4):439-51
pubmed: 19240132
Nat Commun. 2019 Apr 29;10(1):1931
pubmed: 31036804
Cell Rep. 2020 Jan 21;30(3):820-835.e10
pubmed: 31968256
Dev Growth Differ. 2019 Jun;61(5):343-352
pubmed: 30780195
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nucleic Acids Res. 2016 Jan 4;44(D1):D164-71
pubmed: 26438538
Genetics. 2007 Aug;176(4):2099-108
pubmed: 17717194
Mol Cell. 2016 Nov 3;64(3):443-454
pubmed: 27773675
Mol Cell. 2017 Feb 2;65(3):432-446.e5
pubmed: 28157505
Elife. 2012 Dec 18;1:e00205
pubmed: 23256043
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
Nat Struct Mol Biol. 2010 Feb;17(2):194-201
pubmed: 20098423
Elife. 2016 Jun 23;5:
pubmed: 27336723
Nat Genet. 2021 Apr;53(4):477-486
pubmed: 33795867
Mol Cell. 2016 Nov 3;64(3):455-466
pubmed: 27773677
Nat Genet. 2021 Jan;53(1):100-109
pubmed: 33318687
Genes Dev. 2019 Jul 1;33(13-14):799-813
pubmed: 31171700
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10208-10213
pubmed: 28855340
Cell Cycle. 2016 Jun 2;15(11):1479-93
pubmed: 27096886
Nat Rev Mol Cell Biol. 2015 Mar;16(3):155-66
pubmed: 25693131
F1000Res. 2015 Nov 20;4:1310
pubmed: 26835000
Mol Cell. 2004 Jun 4;14(5):637-46
pubmed: 15175158
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Cell Stem Cell. 2017 May 4;20(5):689-705.e9
pubmed: 28285903
Genome Biol. 2015 Dec 01;16:259
pubmed: 26619908
Mol Cell. 2021 Sep 2;81(17):3560-3575.e6
pubmed: 34375585
Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12390-12399
pubmed: 31147463
Trends Biochem Sci. 2005 May;30(5):256-63
pubmed: 15896744
Bioinformatics. 2015 Jun 15;31(12):2032-4
pubmed: 25697820
Dev Cell. 2013 Sep 30;26(6):565-77
pubmed: 24091011
Nat Rev Genet. 2019 Aug;20(8):437-455
pubmed: 31086298
Nat Commun. 2021 Jan 11;12(1):223
pubmed: 33431820
Nat Genet. 2014 Feb;46(2):205-12
pubmed: 24413732