Enhanced nucleosome assembly at CpG sites containing an extended 5-methylcytosine analogue.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
24 06 2022
24 06 2022
Historique:
accepted:
16
05
2022
revised:
05
05
2022
received:
15
10
2021
pubmed:
2
6
2022
medline:
28
6
2022
entrez:
1
6
2022
Statut:
ppublish
Résumé
Methylation of cytosine to 5-methylcytosine (mC) at CpG sites is a prevalent reversible epigenetic mark in vertebrates established by DNA methyltransferases (MTases); the attached methyl groups can alter local structure of DNA and chromatin as well as binding of dedicated proteins. Nucleosome assembly on methylated DNA has been studied extensively, however little is known how the chromatin structure is affected by larger chemical variations in the major groove of DNA. Here, we studied the nucleosome formation in vitro on DNA containing an extended 5mC analog, 5-(6-azidohex-2-ynyl)cytosine (ahyC) installed at biological relevant CpG sites. We found that multiple ahyC residues on 80-Widom and Hsp70 promoter DNA fragments proved compatible with nucleosome assembly. Moreover, unlike mC, ahyC increases the affinity of histones to the DNA, partially altering nucleosome positioning, stability, and the action of chromatin remodelers. Based on molecular dynamics calculations, we suggest that these new features are due to increased DNA flexibility at ahyC-modified sites. Our findings provide new insights into the biophysical behavior of modified DNA and open new ways for directed design of synthetic nucleosomes.
Identifiants
pubmed: 35648439
pii: 6596862
doi: 10.1093/nar/gkac444
pmc: PMC9226530
doi:
Substances chimiques
Chromatin
0
Nucleosomes
0
5-Methylcytosine
6R795CQT4H
Cytosine
8J337D1HZY
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6549-6561Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Nucleic Acids Res. 2012 Dec;40(22):11594-602
pubmed: 23042683
Nanoscale. 2020 Oct 15;12(39):20287-20291
pubmed: 33001091
Nature. 1994 Feb 10;367(6463):525-32
pubmed: 8107823
Cell. 2015 Mar 12;160(6):1135-44
pubmed: 25768909
Nucleic Acids Res. 1982 Apr 24;10(8):2709-21
pubmed: 7079182
Q Rev Biophys. 2001 Aug;34(3):269-324
pubmed: 11838235
Cell. 2004 Jan 23;116(2):259-72
pubmed: 14744436
Genome Biol. 2018 Nov 19;19(1):200
pubmed: 30454035
Curr Opin Chem Biol. 2018 Aug;45:35-47
pubmed: 29501025
J Chem Theory Comput. 2012 Jan 10;8(1):348-362
pubmed: 22368531
Nature. 1997 Sep 18;389(6648):251-60
pubmed: 9305837
Epigenetics Chromatin. 2017 Apr 11;10:18
pubmed: 28413449
J Mol Biol. 2020 Nov 20;432(23):6157-6167
pubmed: 33065111
Biophys J. 2012 Dec 19;103(12):2502-12
pubmed: 23260052
J Comput Chem. 2005 Dec;26(16):1701-18
pubmed: 16211538
Biophys J. 2021 Jun 1;120(11):2148-2155
pubmed: 33838135
Nucleic Acids Res. 2003 Sep 1;31(17):5108-21
pubmed: 12930962
ACS Chem Biol. 2013;8(6):1134-9
pubmed: 23557731
Nat Commun. 2013;4:2190
pubmed: 23877302
J Phys Chem A. 2020 Jul 30;124(30):6246-6253
pubmed: 32614187
Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9):
pubmed: 24003213
Nat Chem Biol. 2009 Jun;5(6):400-2
pubmed: 19430486
Mol Cell. 2020 Aug 6;79(3):371-375
pubmed: 32763226
PLoS Genet. 2014 Mar 20;10(3):e1004157
pubmed: 24651573
Sci Rep. 2017 Oct 6;7(1):12734
pubmed: 28986581
Mol Cell. 2017 Feb 2;65(3):554-564.e6
pubmed: 28111014
PLoS One. 2015 Oct 23;10(10):e0140076
pubmed: 26496704
Biophys J. 2012 May 2;102(9):2140-8
pubmed: 22824278
Oncogene. 2013 Nov 21;32(47):5421-8
pubmed: 23686312
Nucleic Acids Res. 2011 Sep 1;39(16):6956-69
pubmed: 21622955
J Mol Biol. 1991 Jul 5;220(1):101-10
pubmed: 2067009
Genes (Basel). 2015 Jun 12;6(2):299-324
pubmed: 26075616
Biophys J. 2000 Aug;79(2):601-13
pubmed: 10919995
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3074-9
pubmed: 11248034
J Mol Biol. 1998 Feb 13;276(1):19-42
pubmed: 9514715
Nature. 2003 May 8;423(6936):145-50
pubmed: 12736678
Bioinformatics. 2015 Aug 1;31(15):2583-5
pubmed: 25838463
Genome Res. 2014 Aug;24(8):1285-95
pubmed: 24812327
Nucleic Acids Res. 2019 Jul 9;47(12):e68
pubmed: 30918971
EMBO Rep. 2017 Oct;18(10):1697-1706
pubmed: 28801535
Science. 1991 Oct 11;254(5029):238-45
pubmed: 1718039
J Mol Biol. 2007 Aug 17;371(3):725-38
pubmed: 17585938
Open Biol. 2015 Oct;5(10):
pubmed: 26446621
Nat Commun. 2016 Feb 24;7:10813
pubmed: 26905257
Clin Epigenetics. 2020 Oct 20;12(1):153
pubmed: 33081811