Maternal H3K27me3 controls DNA methylation-independent genomic imprinting

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 (ICRs). How parental chromatin becomes equalized and how ICRs escape from this reprogramming is largely unknown. Here we profiled parental allele-specific DNase I hypersensitive sites (DHSs) in mouse zygotes and morula embryos, and investigated the epigenetic mechanisms underlying allelic DHSs. Integrated analyses of DNA methylome and H3K27me3 ChIP-seq data sets revealed 76 genes with paternal allele-specific DHSs that are devoid of DNA methylation but harbor maternal allele-specific H3K27me3. Interestingly, these genes are paternally expressed in preimplantation embryos, and ectopic removal of H3K27me3 induces maternal allele expression. H3K27me3-dependent imprinting is largely lost in the embryonic cell lineage, but at least 5 genes maintain their imprinting in the extra-embryonic cell lineage. The 5 genes include all previously identified DNA methylation-independent imprinted autosomal genes. Thus, our study identifies maternal H3K27me3 as a DNA methylation-independent imprinting mechanism.