Genome-wide maps of H3K4me3 in C57BL6/J, DBA/2J, and BXD lines for male germ cells, hepatocytes, cardiomyocytes, and mouse ESCs

Here, we have explored how natural genetic variation in mice shapes the epigenome by studying levels of H3K4me3, a mark of active chromatin. We found tissue-specific trans-regulation in four diverse cell types: male germ cells, embryonic stem (ES) cells, hepatocytes and cardiomyocytes. Using recombinant inbred lines, we mapped six major trans-acting histone quantitative trait loci (hQTL) modulating hundreds of H3K4me3 sites in germ cells. These loci act dominantly to suppress H3K4me3, which at recombination hotspots reduces the likelihood of subsequent DNA double-strand breaks during meiosis. QTL 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. Measure H3K4me3 levels using ChIP-seq in founders and progeny of a genetic reference population of mice for QTL mapping