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Natural variation of histone modification and its impact on gene expression in the rat genome

C. Rintisch, M. Heinig, A. Bauerfeind, S. Schafer, C. Mieth, G. Patone, O. Hummel, W. Chen, S. Cook, E. Cuppen, M. Colomé-Tatché, F. Johannes, RC. Jansen, H. Neil, M. Werner, M. Pravenec, M. Vingron, N. Hubner,

. 2014 ; 24 (6) : 942-53.

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc15014336
E-zdroje Online Plný text

NLK Free Medical Journals od 1991 do Před 6 měsíci
Freely Accessible Science Journals od 1991-08-01 do Před 1 rokem
PubMed Central od 1997 do Před 6 měsíci
Europe PubMed Central od 1997 do Před 6 měsíci
Open Access Digital Library od 1991-08-01
Open Access Digital Library od 1991-08-01

Odkazy

PubMed 24793478
DOI 10.1101/gr.169029.113
Knihovny.cz E-zdroje

Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. Little is known about interindividual variability of histone modification levels across the genome and to what extent they are influenced by genetic variation. We annotated the rat genome with histone modification maps, identified differences in histone trimethyl-lysine levels among strains, and described their underlying genetic basis at the genome-wide scale using ChIP-seq in heart and liver tissues in a panel of rat recombinant inbred and their progenitor strains. We identified extensive variation of histone methylation levels among individuals and mapped hundreds of underlying cis- and trans-acting loci throughout the genome that regulate histone methylation levels in an allele-specific manner. Interestingly, most histone methylation level variation was trans-linked and the most prominent QTL identified influenced H3K4me3 levels at 899 putative promoters throughout the genome in the heart. Cis- acting variation was enriched in binding sites of distinct transcription factors in heart and liver. The integrated analysis of DNA variation together with histone methylation and gene expression levels showed that histoneQTLs are an important predictor of gene expression and that a joint analysis significantly enhanced the prediction of gene expression traits (eQTLs). Our data suggest that genetic variation has a widespread impact on histone trimethylation marks that may help to uncover novel genotype-phenotype relationships.

Citace poskytuje Crossref.org

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