Journal Article

Maternal H3K27me3 controls DNA methylation-independent imprinting

Inoue, Azusa, Jiang, Lan, Lu, Falong, Zhang, Yi, Suzuki, Tsukasa

2017

Overview

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. Analysis of parental allele-specific chromatin accessibility genome-wide in mouse zygotes and morula embryos, and investigation of the epigenetic mechanisms underlying these allelic sites, identifying maternal H3K27me3 as a DNA methylation-independent mechanism for genomic imprinting. Non-canonical genomic imprinting After fertilization in mammals, there is asymmetry in the epigenetic landscapes of paternal and maternal chromatin, which becomes largely equalized during subsequent development with the exception of imprinted genes. Here, Yi Zhang and colleagues have profiled parental allele-specific chromatin accessibility genome-wide in zygotes and morula embryos, together with analysing DNA methylation and histone H3K27me3 patterns. They find that H3K27me3 is a DNA-methylation-independent mechanism for repression of the maternal allele in genomic imprinting and can identify novel imprinted genes that are dependent on this non-canonical mechanism.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/15 / 38/23 / 38/91 / 631/136/2442 / 631/208/176/1968 / 64/60 / Alleles / Analysis / Animals / Bioinformatics / Blastocyst - metabolism / Cell Lineage / Chromatin / Chromatin - metabolism / Deoxyribonuclease / Deoxyribonuclease I - metabolism / Deoxyribonucleic acid / DNA / DNA - genetics / DNA - metabolism / DNA binding proteins / DNA Methylation / DNA synthesis / Embryo, Mammalian - cytology / Embryo, Mammalian - metabolism / Embryos / Epigenetics / Female / Fertilization / Gene expression / Gene Expression Regulation / Gene loci / Gene sequencing / Genes / Genomes / Genomic Imprinting / Histone H3 / Histones - chemistry / Histones - metabolism / Humanities and Social Sciences / Immunoprecipitation / Lysine / Lysine - metabolism / Male / Methylation / Mice / Morula - metabolism / multidisciplinary / Oocytes / Oocytes - metabolism / Science / Sperm / Stem cells / Zygote - cytology / Zygote - metabolism / Zygotes