Aberrant DNA hydroxymethylation reshapes transcription factor binding in myeloid neoplasms.
DNA hydroxymethylation
Myeloid neoplasms
TET2
Transcription factor
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
28 06 2022
28 06 2022
Historique:
received:
30
01
2022
accepted:
05
06
2022
entrez:
28
6
2022
pubmed:
29
6
2022
medline:
1
7
2022
Statut:
epublish
Résumé
Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of myeloid neoplasms. Here, we report systematic genome-wide mapping of the DNA hydroxymethylomes in over 70 patients with myeloid neoplasms. Our integrative analysis leads to the identification of distinct 5hmC signatures that can sensitively discriminate patients from healthy individuals. At the molecular level, we unveiled dynamic 5hmC changes within key transcription factor (e.g., the CEBP family) binding motifs that are essential for hematopoiesis and myeloid lineage specification. 5hmC redistribution was found to alter the genome-wide binding of CEBP-α, thereby reprogramming transcriptional outputs to affect leukemia cell survival and stemness. Taken together, we provide a comprehensive 5hmC atlas representative of myeloid neoplasms, which sets the stage for future exploration on the epigenetic etiology of hematological malignancies. Mechanistically, our study further furnishes important insights into how abnormal 5hmC distribution in patients directly interrupts the binding of transcription factors to reshape transcriptional landscapes and aggravate leukemogenesis.
Identifiants
pubmed: 35765052
doi: 10.1186/s13148-022-01297-5
pii: 10.1186/s13148-022-01297-5
pmc: PMC9241241
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
81Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL134780
Pays : United States
Organisme : NIGMS NIH HHS
ID : R21 GM138824
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA232017
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146852
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA240258
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA265748
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Nucleic Acids Res. 2019 Sep 19;47(16):8388-8398
pubmed: 31226215
Nature. 2011 May 19;473(7347):394-7
pubmed: 21552279
Leukemia. 2020 Mar;34(3):872-881
pubmed: 31719677
Science. 2017 May 5;356(6337):
pubmed: 28473536
Cancer Cell. 2017 Jul 10;32(1):27-41.e4
pubmed: 28625481
Science. 2009 May 15;324(5929):930-5
pubmed: 19372391
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Mol Cell. 2014 Jun 5;54(5):879-86
pubmed: 24813944
Oncotarget. 2016 Apr 26;7(17):24326-38
pubmed: 27014907
Nat Genet. 2012 Nov;44(11):1179-81
pubmed: 23001125
Mol Cell. 2015 Feb 19;57(4):662-673
pubmed: 25601757
Biochim Biophys Acta. 2015 Jun;1849(6):583-9
pubmed: 25779641
BMC Bioinformatics. 2009 Jul 27;10:232
pubmed: 19635165
Nature. 2015 Sep 24;525(7570):543-547
pubmed: 26367798
Nature. 2016 Jan 7;529(7584):110-4
pubmed: 26700815
Blood. 2007 Apr 15;109(8):3451-61
pubmed: 17170124
Genome Biol. 2014;15(12):550
pubmed: 25516281
Trends Genet. 2014 Oct;30(10):464-74
pubmed: 25132561
J Mol Biol. 2019 Oct 15;:
pubmed: 31626807
Curr Drug Targets. 2017;18(10):1142-1151
pubmed: 28031014
Nat Protoc. 2012 Oct;7(10):1897-908
pubmed: 23018193
Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9920-5
pubmed: 23716660
J Exp Med. 2014 Jan 13;211(1):1-4
pubmed: 24395889
Nature. 2010 Dec 9;468(7325):839-43
pubmed: 21057493
Nat Commun. 2015 Nov 26;6:10071
pubmed: 26607761
Nat Genet. 2016 Apr;48(4):417-26
pubmed: 26928226
Curr Protoc Mol Biol. 2015 Jan 05;109:21.29.1-21.29.9
pubmed: 25559105
Nat Neurosci. 2011 Oct 30;14(12):1607-16
pubmed: 22037496
Cell Rep. 2012 Sep 27;2(3):568-79
pubmed: 22999938
Cancer Cell. 2010 Dec 14;18(6):553-67
pubmed: 21130701
Nucleic Acids Res. 2018 Apr 6;46(6):2883-2900
pubmed: 29394393
Cancer Cell. 2011 Jul 12;20(1):11-24
pubmed: 21723200
Cancer Discov. 2017 Aug;7(8):868-883
pubmed: 28408400
Nucleic Acids Res. 2017 Mar 17;45(5):2396-2407
pubmed: 27903915
Genes Dev. 2016 Apr 1;30(7):733-50
pubmed: 27036965
Cancer Cell. 2011 Jul 12;20(1):25-38
pubmed: 21723201
Cell. 2017 Sep 7;170(6):1079-1095.e20
pubmed: 28823558
Nat Med. 2014 Dec;20(12):1472-8
pubmed: 25326804
Nat Biotechnol. 2010 May;28(5):495-501
pubmed: 20436461
Elife. 2016 Nov 21;5:
pubmed: 27869616
Nat Commun. 2019 Sep 20;10(1):4297
pubmed: 31541101
Nat Commun. 2020 Dec 2;11(1):6161
pubmed: 33268789
Mol Cell. 2014 Oct 23;56(2):286-297
pubmed: 25263596
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14566-71
pubmed: 21873190
Genome Biol. 2011 Jun 20;12(6):R54
pubmed: 21689397
Nucleic Acids Res. 2019 Feb 28;47(4):1774-1785
pubmed: 30566668
J Biomed Nanotechnol. 2013 Sep;9(9):1607-16
pubmed: 23980508
Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):447-452
pubmed: 29222292
N Engl J Med. 2009 May 28;360(22):2289-301
pubmed: 19474426
Nat Commun. 2020 Oct 19;11(1):5270
pubmed: 33077732
Sci Adv. 2020 Oct 16;6(42):
pubmed: 33067228
Mol Cell. 2021 Jul 15;81(14):2960-2974.e7
pubmed: 34111398