Functional annotation of the cattle genome through systematic discovery and characterization of chromatin states and butyrate-induced variations.
Butyrate
Cattle genome
Chromatin states
Functional annotation
Rumen development
Journal
BMC biology
ISSN: 1741-7007
Titre abrégé: BMC Biol
Pays: England
ID NLM: 101190720
Informations de publication
Date de publication:
16 08 2019
16 08 2019
Historique:
received:
29
05
2019
accepted:
05
08
2019
entrez:
18
8
2019
pubmed:
20
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
The functional annotation of genomes, including chromatin accessibility and modifications, is important for understanding and effectively utilizing the increased amount of genome sequences reported. However, while such annotation has been well explored in a diverse set of tissues and cell types in human and model organisms, relatively little data are available for livestock genomes, hindering our understanding of complex trait variation, domestication, and adaptive evolution. Here, we present the first complete global landscape of regulatory elements in cattle and explore the dynamics of chromatin states in rumen epithelial cells induced by the rumen developmental regulator-butyrate. We established the first global map of regulatory elements (15 chromatin states) and defined their coordinated activities in cattle, through genome-wide profiling for six histone modifications, RNA polymerase II, CTCF-binding sites, DNA accessibility, DNA methylation, and transcriptome in rumen epithelial primary cells (REPC), rumen tissues, and Madin-Darby bovine kidney epithelial cells (MDBK). We demonstrated that each chromatin state exhibited specific enrichment for sequence ontology, transcription, methylation, trait-associated variants, gene expression-associated variants, selection signatures, and evolutionarily conserved elements, implying distinct biological functions. After butyrate treatments, we observed that the weak enhancers and flanking active transcriptional start sites (TSS) were the most dynamic chromatin states, occurred concomitantly with significant alterations in gene expression and DNA methylation, which was significantly associated with heifer conception rate and stature economic traits. Our results demonstrate the crucial role of functional genome annotation for understanding genome regulation, complex trait variation, and adaptive evolution in livestock. Using butyrate to induce the dynamics of the epigenomic landscape, we were able to establish the correlation among nutritional elements, chromatin states, gene activities, and phenotypic outcomes.
Sections du résumé
BACKGROUND
The functional annotation of genomes, including chromatin accessibility and modifications, is important for understanding and effectively utilizing the increased amount of genome sequences reported. However, while such annotation has been well explored in a diverse set of tissues and cell types in human and model organisms, relatively little data are available for livestock genomes, hindering our understanding of complex trait variation, domestication, and adaptive evolution. Here, we present the first complete global landscape of regulatory elements in cattle and explore the dynamics of chromatin states in rumen epithelial cells induced by the rumen developmental regulator-butyrate.
RESULTS
We established the first global map of regulatory elements (15 chromatin states) and defined their coordinated activities in cattle, through genome-wide profiling for six histone modifications, RNA polymerase II, CTCF-binding sites, DNA accessibility, DNA methylation, and transcriptome in rumen epithelial primary cells (REPC), rumen tissues, and Madin-Darby bovine kidney epithelial cells (MDBK). We demonstrated that each chromatin state exhibited specific enrichment for sequence ontology, transcription, methylation, trait-associated variants, gene expression-associated variants, selection signatures, and evolutionarily conserved elements, implying distinct biological functions. After butyrate treatments, we observed that the weak enhancers and flanking active transcriptional start sites (TSS) were the most dynamic chromatin states, occurred concomitantly with significant alterations in gene expression and DNA methylation, which was significantly associated with heifer conception rate and stature economic traits.
CONCLUSION
Our results demonstrate the crucial role of functional genome annotation for understanding genome regulation, complex trait variation, and adaptive evolution in livestock. Using butyrate to induce the dynamics of the epigenomic landscape, we were able to establish the correlation among nutritional elements, chromatin states, gene activities, and phenotypic outcomes.
Identifiants
pubmed: 31419979
doi: 10.1186/s12915-019-0687-8
pii: 10.1186/s12915-019-0687-8
pmc: PMC6698049
doi:
Substances chimiques
Butyrates
0
Chromatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
68Références
Nat Rev Genet. 2011 Apr;12(4):283-93
pubmed: 21358745
Nat Genet. 2018 Mar;50(3):362-367
pubmed: 29459679
Trends Neurosci. 2013 May;36(5):305-12
pubmed: 23384445
Genome Biol. 2009;10(3):R25
pubmed: 19261174
Commun Biol. 2019 Jun 18;2:212
pubmed: 31240250
Bioinformatics. 2011 Jun 1;27(11):1571-2
pubmed: 21493656
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
PLoS One. 2012;7(5):e36940
pubmed: 22615851
Genome Res. 2014 Sep;24(9):1550-7
pubmed: 24963154
Epigenetics. 2011 Feb;6(2):147-52
pubmed: 20935486
Sci Rep. 2018 Sep 13;8(1):13747
pubmed: 30213987
Genome Biol. 2015 Mar 25;16:57
pubmed: 25854118
BMC Genomics. 2016 Feb 27;17:144
pubmed: 26920147
J Cell Mol Med. 2009 Sep;13(9B):2990-3005
pubmed: 19583816
BMC Genomics. 2006 Sep 14;7:234
pubmed: 16972989
Sci Data. 2017 Aug 29;4:170113
pubmed: 28850107
Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209
pubmed: 25830558
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Science. 2013 Aug 2;341(6145):569-73
pubmed: 23828891
Nat Protoc. 2012 Mar 01;7(3):562-78
pubmed: 22383036
Physiol Rev. 1990 Apr;70(2):567-90
pubmed: 2181501
Genome Biol. 2014 Feb 20;15(2):R37
pubmed: 24555846
Genet Sel Evol. 2017 May 12;49(1):44
pubmed: 28499345
Sci Rep. 2018 Jun 19;8(1):9345
pubmed: 29921979
Elife. 2017 Mar 20;6:
pubmed: 28318489
Nat Rev Genet. 2019 Mar;20(3):135-156
pubmed: 30514919
BMC Genet. 2016 Jan 05;17:11
pubmed: 26728402
J Dairy Sci. 1987 May;70(5):983-92
pubmed: 3597939
PLoS Genet. 2017 Sep 15;13(9):e1006997
pubmed: 28915238
J Anim Sci. 2019 Feb 1;97(2):909-921
pubmed: 30535158
Annu Rev Anim Biosci. 2019 Feb 15;7:65-88
pubmed: 30427726
BMC Genomics. 2018 Jun 27;19(1):499
pubmed: 29945546
Nature. 2014 Nov 20;515(7527):355-64
pubmed: 25409824
Genetics. 2016 Aug;203(4):1901-13
pubmed: 27317683
Nucleic Acids Res. 2013 Jan;41(2):827-41
pubmed: 23221638
Genes Chromosomes Cancer. 2000 Dec;29(4):356-62
pubmed: 11066082
Nat Biotechnol. 2010 Aug;28(8):817-25
pubmed: 20657582
Arch Tierernahr. 1998;51(2-3):165-75
pubmed: 9672714
J Anim Sci. 2005 Jan;83(1):89-97
pubmed: 15583047
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Nature. 2017 Oct 11;550(7675):204-213
pubmed: 29022597
Nucleic Acids Res. 2013 Jan;41(Database issue):D871-9
pubmed: 23180796
Nucleic Acids Res. 2017 Jun 2;45(10):5770-5784
pubmed: 28334816
PLoS One. 2019 Jan 17;14(1):e0210889
pubmed: 30653577
Neuropsychopharmacology. 2013 Jan;38(1):23-38
pubmed: 22781841
Funct Integr Genomics. 2007 Jul;7(3):193-205
pubmed: 17186197
Genome Biol. 2012 Oct 03;13(10):R87
pubmed: 23034086
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Bioinformatics. 2011 Jan 15;27(2):225-31
pubmed: 21098430
Funct Integr Genomics. 2012 Mar;12(1):119-30
pubmed: 22249597
Nat Methods. 2012 Feb 28;9(3):215-6
pubmed: 22373907
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nat Neurosci. 2011 Mar;14(3):279-84
pubmed: 21278731
Methods Mol Biol. 2017;1510:77-91
pubmed: 27761814
Commun Biol. 2019 Mar 14;2:100
pubmed: 30886909
J Dairy Sci. 2011 Nov;94(11):5578-88
pubmed: 22032381
BMC Genomics. 2017 Aug 10;18(1):604
pubmed: 28797230
Gene Regul Syst Bio. 2018 May 09;12:1177625018774798
pubmed: 29785087
Annu Rev Genomics Hum Genet. 2006;7:29-59
pubmed: 16719718
Gene. 2015 May 10;562(1):8-15
pubmed: 25701602
Mol Carcinog. 2006 Jun;45(6):443-6
pubmed: 16652377
Sci Immunol. 2016 Sep 23;1(3):eaaf8665
pubmed: 28783680
Sci Rep. 2017 May 25;7(1):2413
pubmed: 28546557
Mol Biol Evol. 2015 Mar;32(3):711-25
pubmed: 25431480
Curr Drug Targets. 2006 Apr;7(4):443-52
pubmed: 16611031
Genome Biol. 2016 Jul 05;17(1):150
pubmed: 27380908
Nat Commun. 2018 Feb 28;9(1):859
pubmed: 29491421
Science. 2004 Oct 22;306(5696):636-40
pubmed: 15499007
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Stem Cell Reports. 2017 Jul 11;9(1):397-407
pubmed: 28648898
Carcinogenesis. 2006 Feb;27(2):344-9
pubmed: 16267097
Neuropharmacology. 2011 Jun;60(7-8):1109-15
pubmed: 20888352
Epigenetics. 2019 Mar;14(3):260-276
pubmed: 30810461
BMC Biol. 2019 Aug 16;17(1):68
pubmed: 31419979