Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin.
Epigenetics
Mathematical biosciences
Systems biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
23 Jul 2021
23 Jul 2021
Historique:
received:
24
02
2021
revised:
23
05
2021
accepted:
08
06
2021
entrez:
19
7
2021
pubmed:
20
7
2021
medline:
20
7
2021
Statut:
epublish
Résumé
Bivalent chromatin is characterized by occupation of both activating and repressive histone modifications. Here, we develop a mathematical model that involves antagonistic histone modifications H3K4me3 and H3K27me3 to capture the key features of bivalent chromatin. Three necessary conditions for the emergence of bivalent chromatin are identified, including advantageous methylating activity over demethylating activity, frequent noise conversions of modifications, and sufficient nonlinearity. The first condition is further confirmed by analyzing the existing experimental data. Investigation of the composition of bivalent chromatin reveals that bivalent nucleosomes carrying both H3K4me3 and H3K27me3 account for no more than half of nucleosomes at the bivalent chromatin domain. We identify that bivalent chromatin not only allows transitions to multiple states but also serves as a stepping stone to facilitate a stepwise transition between repressive chromatin state and activating chromatin state and thus elucidate crucial roles of bivalent chromatin in mediating phenotypical plasticity during cell fate determination.
Identifiants
pubmed: 34278251
doi: 10.1016/j.isci.2021.102732
pii: S2589-0042(21)00700-8
pmc: PMC8261666
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102732Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Cell Rep. 2013 Jun 27;3(6):1777-84
pubmed: 23727241
Cell. 2007 May 18;129(4):813-22
pubmed: 17512413
Nat Biotechnol. 2016 Sep;34(9):953-61
pubmed: 27454738
Nat Commun. 2016 Aug 17;7:12514
pubmed: 27530917
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2989-94
pubmed: 22323599
Cell Syst. 2017 Apr 26;4(4):445-457.e8
pubmed: 28342717
Cell. 2005 Jun 17;121(6):859-72
pubmed: 15960974
Nat Cell Biol. 2008 Nov;10(11):1291-300
pubmed: 18931660
Phys Rev Lett. 2014 Feb 14;112(6):068101
pubmed: 24580708
Mol Cell. 2017 Apr 20;66(2):247-257.e5
pubmed: 28410996
Nat Commun. 2019 May 13;10(1):2133
pubmed: 31086177
Cell. 2007 Feb 23;128(4):707-19
pubmed: 17320508
Cancer Cell. 2013 May 13;23(5):677-92
pubmed: 23680150
Cell. 2007 Feb 23;128(4):693-705
pubmed: 17320507
Cell Stem Cell. 2011 Jul 8;9(1):24-36
pubmed: 21726831
Nature. 2007 Oct 11;449(7163):731-4
pubmed: 17713478
Mol Cell. 2007 Jan 12;25(1):15-30
pubmed: 17218268
Nature. 2016 Sep 22;537(7621):558-562
pubmed: 27626379
Science. 2007 Oct 19;318(5849):447-50
pubmed: 17761849
PLoS One. 2013 Nov 01;8(11):e77944
pubmed: 24223747
BMC Med Genomics. 2016 Sep 15;9(1):60
pubmed: 27634286
Nat Struct Mol Biol. 2006 Aug;13(8):713-9
pubmed: 16878130
Nat Cell Biol. 2006 May;8(5):532-8
pubmed: 16570078
Epigenetics Chromatin. 2017 Sep 25;10(1):45
pubmed: 28946896
Development. 2009 Nov;136(21):3531-42
pubmed: 19820181
Cell. 2006 Apr 21;125(2):315-26
pubmed: 16630819
Cell Rep. 2016 Nov 15;17(8):2112-2124
pubmed: 27851972
Science. 2016 May 6;352(6286):717-21
pubmed: 27151869
Genes Dev. 2013 Jun 15;27(12):1318-38
pubmed: 23788621
Nature. 2009 Oct 8;461(7265):762-7
pubmed: 19767730
BMC Syst Biol. 2018 Feb 27;12(1):22
pubmed: 29486740
Mol Cell. 2018 Oct 18;72(2):239-249.e5
pubmed: 30146316
Trends Genet. 2016 Jan;32(1):42-56
pubmed: 26704082
Nat Rev Mol Cell Biol. 2011 Nov 23;12(12):799-814
pubmed: 22108599
Cell Syst. 2019 Sep 25;9(3):271-285.e7
pubmed: 31542414
Genes Dev. 2008 May 15;22(10):1345-55
pubmed: 18483221
Mol Cell Biol. 2007 Mar;27(5):1889-903
pubmed: 17178841
Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10783-90
pubmed: 20479220
Cell. 2012 Sep 28;151(1):181-93
pubmed: 23021224
Mol Cell. 2015 Nov 19;60(4):584-96
pubmed: 26590716
Cell. 2013 Jul 3;154(1):61-74
pubmed: 23827675