Distinctive Chromatin in Human Sperm Packages Genes that Guide Embryo Development: ChIP-seq

As nucleosomes are widely replaced by protamine in mature human sperm, epigenetic contributions to embryo development appear limited. However, our genome-wide approaches find nucleosomes at low levels genome-wide, but also significantly enriched at imprinted gene clusters, miRNA clusters, HOX gene clusters, and the promoters of other developmental transcription and signaling factors. Developmental promoters were often DNA hypomethylated, and bore histone modifications localized to discrete locations: H3K4me2 is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX loci, certain non-coding RNAs, and generally to paternally-expressed imprinted loci. In contrast, H3K4me3 is generally absent at paternally-repressed imprinted loci. Interestingly, repressive H3K27me3 is enriched at many developmental promoters that lack early expression in embryos, with significant overlap with bivalent (H3K4me3/H3K27me3) promoters in ES cells. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.