RT Journal Article SR Electronic T1 Tissue-specific trans regulation of the mouse epigenome JF bioRxiv FD Cold Spring Harbor Laboratory SP 322081 DO 10.1101/322081 A1 Christopher L. Baker A1 Michael Walker A1 Seda Arat A1 Guruprasad Ananda A1 Pavlina Petkova A1 Natalie Powers A1 Hui Tian A1 Catrina Spruce A1 Bo Ji A1 Dylan Rausch A1 Kwangbom Choi A1 Petko M. Petkov A1 Gregory W. Carter A1 Kenneth Paigen YR 2018 UL http://biorxiv.org/content/early/2018/05/15/322081.abstract AB Although a variety of writers, readers, and erasers of epigenetic modifications are known, we have little information about the underlying regulatory systems controlling the establishment and maintenance of the epigenetic landscape, which varies greatly among cell types. Here, we have explored how natural genetic variation impacts the epigenome in mice. Studying levels of H3K4me3, a histone modification at sites such as promoters, enhancers, and recombination hotspots, we found tissue-specific trans-regulation of H3K4me3 levels in four highly diverse cell types: male germ cells, embryonic stem (ES) cells, hepatocytes and cardiomyocytes. To identify the genetic loci involved, we measured H3K4me3 levels in male germ cells in a mapping population of 60 BXD recombinant inbred lines, identifying extensive trans-regulation primarily controlled by six major histone quantitative trait loci (hQTL). These chromatin regulatory loci act dominantly to suppress H3K4me3, which at hotspots reduces the likelihood of subsequent DNA double-strand breaks. QTL locations do not correspond with enzyme known to metabolize chromatin features. Instead their locations match clusters of zinc finger genes, making these possible candidates that explain the dominant suppression of H3K4me3. Collectively, these data describe an extensive, tissue-specific set of chromatin regulatory loci that control functionally related chromatin sites.