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Nature. 2017 Jul 27;547(7664):419-424. doi: 10.1038/nature23262. Epub 2017 Jul 19.

Maternal H3K27me3 controls DNA methylation-independent imprinting.

Inoue A1,2,3, Jiang L1,2,3, Lu F1,2,3, Suzuki T1,2,3, Zhang Y1,2,3,4,5.

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Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.


Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashions. After 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 imprinting control regions escape from this reprogramming is largely unknown. Here we profile parental allele-specific DNase I hypersensitive sites in mouse zygotes and morula embryos, and investigate the epigenetic mechanisms underlying these allelic sites. Integrated analyses of DNA methylome and tri-methylation at lysine 27 of histone H3 (H3K27me3) chromatin immunoprecipitation followed by sequencing identify 76 genes with paternal allele-specific DNase I hypersensitive sites that are devoid of DNA methylation but harbour 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 five genes maintain their imprinted expression in the extra-embryonic cell lineage. The five genes include all paternally expressed autosomal imprinted genes previously demonstrated to be independent of oocyte DNA methylation. Thus, our study identifies maternal H3K27me3 as a DNA methylation-independent imprinting mechanism.

[Indexed for MEDLINE]

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