H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts.
Acetylation
Adult
Case-Control Studies
Chromatin
/ metabolism
Epigenomics
/ methods
Female
Heart Failure
/ genetics
Histones
/ metabolism
Humans
Male
Myocardium
/ metabolism
Myocytes, Cardiac
/ metabolism
RNA Polymerase II
/ metabolism
RNA, Messenger
/ metabolism
Transcription Factors
Transcriptome
/ genetics
Ventricular Remodeling
/ genetics
Histone acetylation
Myocardial remodeling
Transcription factor
Transcriptome
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
14 07 2020
14 07 2020
Historique:
received:
06
04
2020
accepted:
30
06
2020
entrez:
16
7
2020
pubmed:
16
7
2020
medline:
19
8
2021
Statut:
epublish
Résumé
H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes. We detected chromatin regions with differential acetylation activity (DARs; P Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles, we further provide promising TF-encoding genes that could serve as master regulators of myocardial remodeling. Combined, our findings highlight the important role of chromatin regulatory signatures in understanding disease etiology.
Sections du résumé
BACKGROUND
H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes.
RESULTS
We detected chromatin regions with differential acetylation activity (DARs; P
CONCLUSIONS
Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles, we further provide promising TF-encoding genes that could serve as master regulators of myocardial remodeling. Combined, our findings highlight the important role of chromatin regulatory signatures in understanding disease etiology.
Identifiants
pubmed: 32664951
doi: 10.1186/s13148-020-00895-5
pii: 10.1186/s13148-020-00895-5
pmc: PMC7362435
doi:
Substances chimiques
Chromatin
0
Histones
0
RNA, Messenger
0
Transcription Factors
0
RNA Polymerase II
EC 2.7.7.-
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
106Subventions
Organisme : Department of Health
ID : DRF-2013-06-102
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/35/34374
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S003754/1
Pays : United Kingdom
Références
J Am Coll Cardiol. 2004 Jul 21;44(2):398-405
pubmed: 15261938
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Circ Heart Fail. 2011 Jan;4(1):5-7
pubmed: 21245455
Nat Rev Genet. 2014 Apr;15(4):272-86
pubmed: 24614317
Acta Biomater. 2019 Apr 15;89:180-192
pubmed: 30862552
Cardiovasc Res. 2011 Feb 1;89(2):265-72
pubmed: 20880837
Nat Commun. 2016 Sep 28;7:12983
pubmed: 27677335
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20164-9
pubmed: 24284169
Nat Commun. 2018 Jan 26;9(1):391
pubmed: 29374152
Nucleic Acids Res. 2012 Jan;40(1):148-58
pubmed: 21914722
Genome Biol. 2010;11(12):R124
pubmed: 21182765
Nat Commun. 2018 Nov 22;9(1):4934
pubmed: 30467383
Nat Commun. 2018 Jan 9;9(1):120
pubmed: 29317621
Circulation. 2010 Dec 21;122(25):2727-35
pubmed: 21173361
Nat Biotechnol. 2008 Nov;26(11):1293-300
pubmed: 18978777
Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1419
pubmed: 29485202
Nature. 2017 Dec 7;552(7683):110-115
pubmed: 29160304
Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52
pubmed: 25352553
Card Fail Rev. 2015 Oct;1(2):64-68
pubmed: 28785434
Circulation. 2013 Jul 23;128(4):388-400
pubmed: 23877061
Nat Genet. 2008 May;40(5):546-52
pubmed: 18443592
BMC Bioinformatics. 2010 Apr 01;11:165
pubmed: 20356413
Basic Res Cardiol. 2011 Nov;106(6):1269-81
pubmed: 22057716
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Commun. 2018 Nov 19;9(1):4877
pubmed: 30451828
Nat Commun. 2013;4:2203
pubmed: 23892279
Genome Biol. 2017 Sep 14;18(1):170
pubmed: 28903782
Epigenomics. 2017 Jan;9(1):47-55
pubmed: 27936932
Biol Sex Differ. 2019 Feb 4;10(1):7
pubmed: 30717770
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2926-31
pubmed: 20133639
Mol Med Rep. 2016 Dec;14(6):5573-5586
pubmed: 27840985
Curr Protoc Mol Biol. 2010 Jul;Chapter 21:Unit 21.19.1-14
pubmed: 20583098
Nat Commun. 2018 Oct 30;9(1):4435
pubmed: 30375404
Nat Rev Mol Cell Biol. 2019 Jun;20(6):327-337
pubmed: 30886333
Cell Res. 2011 Mar;21(3):381-95
pubmed: 21321607
Cell. 2016 Nov 17;167(5):1385-1397.e11
pubmed: 27863250
Physiol Rev. 2017 Jan;97(1):1-37
pubmed: 27807199
Mol Cell Biol. 2015 Dec 28;36(5):809-19
pubmed: 26711262
Cells. 2019 Dec 11;8(12):
pubmed: 31835742
Fibrogenesis Tissue Repair. 2012 Sep 03;5(1):15
pubmed: 22943504
Eur J Heart Fail. 2014 Nov;16(11):1160-7
pubmed: 25287281
Cell Rep. 2018 Jan 16;22(3):600-610
pubmed: 29346760
Cardiovasc Res. 2017 Jun 1;113(7):725-736
pubmed: 28460026
Cells. 2020 Jan 08;9(1):
pubmed: 31936297
Trends Genet. 2016 Apr;32(4):225-237
pubmed: 26862051
Circulation. 2017 Oct 24;136(17):1613-1625
pubmed: 28802249
Epigenetics. 2015;10(6):460-6
pubmed: 25941994
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Ann Ist Super Sanita. 2016 Apr-Jun;52(2):223-9
pubmed: 27364397
Trends Biochem Sci. 2017 Dec;42(12):977-989
pubmed: 29122461
Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2301-2306
pubmed: 28193859
Nat Commun. 2017 Nov 20;8(1):1614
pubmed: 29158499
J Biol Chem. 2019 Nov 15;294(46):17693-17706
pubmed: 31594864
J Mol Cell Cardiol. 2014 Dec;77:168-74
pubmed: 25451387
Genomics Proteomics Bioinformatics. 2016 Aug;14(4):207-15
pubmed: 27431744
Circulation. 2017 Oct 17;136(16):1528-1544
pubmed: 28838933
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
pubmed: 23401516
Science. 2012 May 11;336(6082):736-9
pubmed: 22499810
J Mol Cell Cardiol. 2002 Jul;34(7):739-48
pubmed: 12099714
Nature. 2012 Apr 12;484(7393):S9
pubmed: 22509510
Genome Biol. 2016 Apr 28;17:77
pubmed: 27121950
PLoS One. 2017 May 5;12(5):e0177242
pubmed: 28475616
BMC Evol Biol. 2015 Nov 20;15:259
pubmed: 26589719
Biomed Res Int. 2015;2015:105620
pubmed: 26221581
Nucleic Acids Res. 2013 Jan;41(Database issue):D56-63
pubmed: 23193274
Arch Cardiovasc Dis. 2017 Jan;110(1):26-34
pubmed: 27839677
Circ Res. 2018 Jan 5;122(1):167-183
pubmed: 29301848
Hypertension. 2007 Mar;49(3):401-7
pubmed: 17242305
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
pubmed: 19465376
Proteomics Clin Appl. 2016 Jan;10(1):84-91
pubmed: 26280680
Stem Cell Reports. 2018 Mar 13;10(3):794-807
pubmed: 29456183
Mayo Clin Proc. 2020 Apr;95(4):688-697
pubmed: 31954524