Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.
DNA methylation
DNMT1
H3K9me3
allosteric regulation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
04 08 2020
04 08 2020
Historique:
pubmed:
18
7
2020
medline:
2
10
2020
entrez:
18
7
2020
Statut:
ppublish
Résumé
In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.
Identifiants
pubmed: 32675241
pii: 2009316117
doi: 10.1073/pnas.2009316117
pmc: PMC7414182
doi:
Substances chimiques
Heterochromatin
0
Histones
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
DNMT1 protein, human
EC 2.1.1.37
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18439-18447Subventions
Organisme : NCI NIH HHS
ID : T32 CA009302
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA198279
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215284
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211336
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 ES101965
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM079641
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM126900
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119721
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201268
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA210072
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009156
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI153419
Pays : United States
Déclaration de conflit d'intérêts
Competing interest statement: O.G. and B.D.S are cofounders of EpiCypher, Inc.
Références
Genome Res. 2008 Dec;18(12):1969-78
pubmed: 18971312
Nature. 1993 Nov 25;366(6453):362-5
pubmed: 8247133
Nat Commun. 2016 Apr 05;7:11197
pubmed: 27045799
Chembiochem. 2011 Jan 24;12(2):206-22
pubmed: 21243710
Biochemistry. 2005 Nov 15;44(45):14977-88
pubmed: 16274244
Nat Genet. 1998 Oct;20(2):116-7
pubmed: 9771701
J Mol Biol. 2015 Jul 31;427(15):2520-2531
pubmed: 26070743
Science. 2007 Sep 21;317(5845):1760-4
pubmed: 17673620
J Biol Chem. 2011 Apr 29;286(17):15344-51
pubmed: 21389349
Nat Commun. 2015 May 11;6:7023
pubmed: 25960197
Nat Rev Genet. 2009 May;10(5):295-304
pubmed: 19308066
Nat Rev Genet. 2009 Nov;10(11):805-11
pubmed: 19789556
Epigenetics. 2009 Jan;4(1):8-14
pubmed: 19077538
Nat Rev Genet. 2005 Aug;6(8):597-610
pubmed: 16136652
Cell. 2011 Dec 23;147(7):1511-24
pubmed: 22196728
Nature. 2007 Dec 6;450(7171):908-12
pubmed: 17994007
Nat Rev Mol Cell Biol. 2015 Sep;16(9):519-32
pubmed: 26296162
Science. 2016 Feb 12;351(6274):725-8
pubmed: 26912860
Nucleic Acids Res. 2018 Apr 6;46(6):3218-3231
pubmed: 29471350
Nucleic Acids Res. 2011 Oct;39(19):8355-65
pubmed: 21745816
Mol Cell Biol. 2008 Jan;28(2):705-17
pubmed: 17967883
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9055-9
pubmed: 21518897
Nat Commun. 2013;4:1563
pubmed: 23463006
Genes Cells. 2006 Jul;11(7):805-14
pubmed: 16824199
J Cell Biochem. 2011 Feb;112(2):439-44
pubmed: 21268065
Biochemistry. 2010 Apr 13;49(14):2999-3008
pubmed: 20210320
Cell. 1998 May 1;93(3):305-8
pubmed: 9590161
Curr Biol. 2003 Jul 15;13(14):1192-200
pubmed: 12867029
Sci Rep. 2017 Dec;7(1):55
pubmed: 28246399
Mol Cell. 2017 Oct 19;68(2):350-360.e7
pubmed: 29053958
Cell. 2012 Sep 28;151(1):167-80
pubmed: 23021223
Chembiochem. 2014 Mar 21;15(5):743-8
pubmed: 24532244
Genes Dev. 2013 Jun 1;27(11):1288-98
pubmed: 23752590
Elife. 2016 Sep 06;5:
pubmed: 27595565
Nature. 2013 Oct 10;502(7470):249-53
pubmed: 24013172
Epigenetics. 2006 Apr-Jun;1(2):63-6
pubmed: 17965604
Epigenetics Chromatin. 2015 Jan 15;8:3
pubmed: 25788984
Biochem Biophys Res Commun. 2019 Aug 20;516(2):578-583
pubmed: 31235252
Sci Signal. 2010 Nov 02;3(146):ra80
pubmed: 21045206
Cell. 2001 Nov 2;107(3):323-37
pubmed: 11701123
Mol Cell. 2004 Feb 13;13(3):427-34
pubmed: 14967149
Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12950-5
pubmed: 22837395
Nat Struct Mol Biol. 2012 Nov;19(11):1155-60
pubmed: 23022729
ACS Chem Biol. 2019 Oct 18;14(10):2315-2326
pubmed: 31479228
J Mol Biol. 1997 Jul 18;270(3):385-95
pubmed: 9237905
J Biol Chem. 2013 Jan 11;288(2):1329-39
pubmed: 23161542
Nat Commun. 2020 Mar 6;11(1):1222
pubmed: 32144273
Nat Struct Mol Biol. 2007 Nov;14(11):1025-1040
pubmed: 17984965
Nature. 2015 Jan 29;517(7536):640-4
pubmed: 25383530
Science. 2011 Feb 25;331(6020):1036-40
pubmed: 21163962
Science. 2012 Feb 10;335(6069):709-12
pubmed: 22323818
Science. 1997 Sep 26;277(5334):1996-2000
pubmed: 9302295
J Mol Biol. 2012 Jan 13;415(2):318-28
pubmed: 22100450
Nat Rev Genet. 2013 Mar;14(3):204-20
pubmed: 23400093
J Biol Chem. 2014 Jan 3;289(1):379-86
pubmed: 24253042
Annu Rev Biochem. 2005;74:481-514
pubmed: 15952895
Cell Res. 2015 Aug;25(8):911-29
pubmed: 26065575