Allelic genome-wide maps of open chromatin state in zygotes and early embryo

Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashion. Following fertilization, the initially distinct parental epigenomes become largely equalized with the exception of certain loci including imprinting control regions. How parental chromatin becomes equalized and how imprinted genes escape this wave of reprogramming is largely unknown. Here we generated high-resolution maps of parental allele-specific DNase I hypersensitive sites (DHSs) in zygotes and morula embryos by using physically-isolated parental pronuclei, as well as parthenogenetic (PG) and androgenetic (AG) embryos. Allelic transcriptome analyses revealed a high correlation between allelic DHSs and allelic gene expression not only in known imprinted genes but also in dozens of genes not previously known to be imprinted. Interestingly, we found that many paternally- expressed genes harbor paternal allele-specific DHSs (Ps-DHSs) that are highly enriched for histone H3K27 tri-methylation (H3K27me3) but devoid of DNA methylation in maternal allele. Importantly, ectopic removal of the H3K27me3 turns Ps-DHSs into bi- allelic DHSs and induces maternal allele derepression in genes that include maternal DNA methylation-independent imprinted genes Gab1, Sfmbt2, Slc38a4, and Phf17 (also known as Jade1). Thus, our study not only reveals parental allele-specific chromatin accessibility of preimplantation embryos, but also identifies maternal H3K27me3 as a DNA methylation- independent mechanism for genomic imprinting.