RT Journal
A1 Rintisch, Carola
A1 Heinig, Matthias
A1 Bauerfeind, Anja
A1 Schafer, Sebastian
A1 Mieth, Christin
A1 Patone, Giannino
A1 Hummel, Oliver
A1 Chen, Wei
A1 Cook, Stuart
A1 Cuppen, Edwin
A1 Colomé-Tatché, Maria
A1 Johannes, Frank
A1 Jansen, Ritsert C.
A1 Neil, Helen
A1 Werner, Michel
A1 Pravenec, Michal
A1 Vingron, Martin
A1 Hubner, Norbert
T1 Natural variation of histone modification and its impact on gene expression in the rat genome
JF Genome Research 
JO Genome Research 
YR 2014 
FD June 01 
VO 24 
IS 6 
SP 942 
OP 953 
DO 10.1101/gr.169029.113 
UL http://genome.cshlp.org/content/24/6/942.abstract 
AB 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.