Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers.
CREB-Binding Protein
/ genetics
Cell Line, Tumor
Chromatin
/ metabolism
DNA Methylation
/ genetics
Datasets as Topic
E1A-Associated p300 Protein
/ genetics
Gene Expression Regulation, Neoplastic
Gene Silencing
Histones
/ genetics
Humans
Mutation
Neoplasms
/ genetics
Proto-Oncogene Proteins c-myc
/ metabolism
Signal Transduction
/ genetics
Transcription Initiation Site
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 05 2019
16 05 2019
Historique:
received:
02
07
2018
accepted:
09
04
2019
entrez:
18
5
2019
pubmed:
18
5
2019
medline:
8
6
2019
Statut:
epublish
Résumé
Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing. Further analysis identifies a hypermethylated subtype which shows a functional convergence on MYC targets and association with CREBBP/EP300 mutation. The tumor-specific shift to transcriptional repression associated with DNA methylation at TSSs was confirmed in multiple tumor types. Our data may show a common underlying epigenetic dysregulation in cancer associated with broad enrichment of repressive chromatin marks and aberrant DNA hypermethylation at TSSs in combination with MYC network activation.
Identifiants
pubmed: 31097695
doi: 10.1038/s41467-019-09937-w
pii: 10.1038/s41467-019-09937-w
pmc: PMC6522544
doi:
Substances chimiques
Chromatin
0
Histones
0
MYC protein, human
0
Proto-Oncogene Proteins c-myc
0
CREB-Binding Protein
EC 2.3.1.48
CREBBP protein, human
EC 2.3.1.48
E1A-Associated p300 Protein
EC 2.3.1.48
EP300 protein, human
EC 2.3.1.48
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2188Subventions
Organisme : NCI NIH HHS
ID : R33 CA094304
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA194107
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM123313
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA220341
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA222826
Pays : United States
Organisme : NIDCR NIH HHS
ID : P50 DE019032
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009285
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE023347
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217885
Pays : United States
Commentaires et corrections
Type : ErratumIn
Références
Nat Rev Cancer. 2011 Sep 23;11(10):726-34
pubmed: 21941284
Nat Genet. 2009 Feb;41(2):178-186
pubmed: 19151715
Cancer Res. 2017 Oct 1;77(19):5248-5258
pubmed: 28733453
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Nat Rev Mol Cell Biol. 2014 Nov;15(11):703-8
pubmed: 25315270
Genome Biol. 2016 Jan 26;17:11
pubmed: 26813288
Oncogene. 1989 Dec;4(12):1463-8
pubmed: 2687767
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Bioinformatics. 2015 Jun 1;31(11):1724-8
pubmed: 25637560
Nat Rev Genet. 2009 May;10(5):295-304
pubmed: 19308066
J Clin Invest. 2013 Jun;123(6):2488-501
pubmed: 23635773
Clin Cancer Res. 2013 Oct 1;19(19):5444-55
pubmed: 23894057
Int J Cancer. 2016 Jul 15;139(2):373-82
pubmed: 26949921
Clin Cancer Res. 2011 Jul 1;17(13):4225-31
pubmed: 21558408
Nature. 2015 Jan 29;517(7536):576-82
pubmed: 25631445
Nucleic Acids Res. 2016 Feb 18;44(3):1105-17
pubmed: 26464434
Clin Cancer Res. 2011 Jul 1;17(13):4320-30
pubmed: 21551254
BMC Genomics. 2015 Oct 28;16:873
pubmed: 26510534
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
PLoS One. 2014 May 19;9(5):e97818
pubmed: 24842468
Epigenetics. 2014 Jul;9(7):1031-46
pubmed: 24786473
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Nat Rev Cancer. 2014 Jun;14(6):395-405
pubmed: 24854082
Genome Biol. 2014 Feb 20;15(2):R37
pubmed: 24555846
Leukemia. 2012 Aug;26(8):1797-803
pubmed: 22388726
Cancer Discov. 2016 Apr;6(4):430-45
pubmed: 26603525
Epigenetics Chromatin. 2015 Apr 17;8:14
pubmed: 25960768
Genome Biol. 2015 Jul 14;16:140
pubmed: 26169266
Nat Genet. 2009 Dec;41(12):1350-3
pubmed: 19881528
PLoS One. 2013;8(1):e54742
pubmed: 23358896
BMC Genomics. 2011 Jun 13;12:313
pubmed: 21669002
Nat Genet. 2017 Feb;49(2):180-185
pubmed: 28067913
Cell. 2007 Feb 23;128(4):683-92
pubmed: 17320506
EBioMedicine. 2017 Mar;17:223-236
pubmed: 28314692
Genome Res. 2009 Sep;19(9):1639-45
pubmed: 19541911
Nat Struct Mol Biol. 2011 Jul 03;18(8):867-74
pubmed: 21725293
Clin Cancer Res. 2015 Feb 15;21(4):870-81
pubmed: 25492084
Nature. 2009 Nov 5;462(7269):108-12
pubmed: 19847166
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Cancer Res. 2017 Dec 1;77(23):6538-6550
pubmed: 28947419
Nature. 2011 Mar 10;471(7337):189-95
pubmed: 21390126
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17834-9
pubmed: 17093053
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15544-9
pubmed: 25313082
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
PLoS One. 2015 Jun 22;10(6):e0129808
pubmed: 26098903
Nat Biotechnol. 2010 May;28(5):495-501
pubmed: 20436461
Arch Pathol Lab Med. 2015 Nov;139(11):1373-8
pubmed: 25978766
J Virol. 2006 Jun;80(12):5723-32
pubmed: 16731911
PLoS One. 2011;6(5):e20584
pubmed: 21637785
Cell. 1993 Jan 29;72(2):233-45
pubmed: 8425220
Head Neck. 2010 Apr;32(4):417-26
pubmed: 19760794
Cancer. 2014 Jul 1;120(13):2006-15
pubmed: 24705963
Genome Med. 2013 Feb 05;5(2):15
pubmed: 23419152
EMBO J. 2005 Jan 26;24(2):336-46
pubmed: 15616584
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nat Rev Cancer. 2013 Jul;13(7):497-510
pubmed: 23760024
Oncotarget. 2014 Oct 15;5(19):8906-23
pubmed: 25275298
Nat Genet. 2011 Jun 26;43(8):768-75
pubmed: 21706001
Cancer Detect Prev. 2004;28(3):178-86
pubmed: 15225897
Genome Med. 2014 Aug 26;6(8):61
pubmed: 25191524
Genome Res. 2012 Feb;22(2):246-58
pubmed: 22156296
Nucleic Acids Res. 2016 Jun 20;44(11):e108
pubmed: 27060149
Cancer Cell. 2013 Jan 14;23(1):9-22
pubmed: 23245995
Cancer Discov. 2017 Mar;7(3):322-337
pubmed: 28069569