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

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

Genome Res. 24, 942-953 (2014)
DOI PMC
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 0
ISSN (print) / ISBN 1088-9051
e-ISSN 1549-5469
Zeitschrift Genome Research
Quellenangaben Band: 24, Heft: 6, Seiten: 942-953 Artikelnummer: , Supplement: ,
Verlag Cold Spring Harbor Laboratory Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-553500-001
PubMed ID 24793478
DOI 10.1101/gr.169029.113
Erfassungsdatum 2014-12-31
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