PRC2 and EHMT1 regulate H3K27me2 and H3K27me3 establishment across the zygote genome

• Published in: Nature communications Vol. 11; no. 1; pp. 6354 - 12
• Main Authors: Meng, Tie-Gang, Zhou, Qian, Ma, Xue-Shan, Liu, Xiao-Yu, Meng, Qing-Ren, Huang, Xian-Ju, Liu, Hong-Lin, Lei, Wen-Long, Zhao, Zheng-Hui, Ouyang, Ying-Chun, Hou, Yi, Schatten, Heide, Ou, Xiang-Hong, Wang, Zhen-Bo, Gao, Shao-Rong, Sun, Qing-Yuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.12.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 14/19; 38/89; 631/136/2434/1706; 631/208/176; 631/337/100/2285; 64/60; 82/80; Animals; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenetics; Epigenomics; Eukaryotes; Gene silencing; Genome; Genomes; Heterochromatin; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Histones - metabolism; Humanities and Social Sciences; Male; Mammals; Methylation; Mice; Mice, Inbred ICR; Mice, Knockout; Micrococcal Nuclease; multidisciplinary; Nuclease; Oogenesis - physiology; Polycomb Repressive Complex 2 - genetics; Pronucleus; Protein Processing, Post-Translational; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Zygote - metabolism; Zygotes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20242-9

The formation of zygote is the beginning of mammalian life, and dynamic epigenetic modifications are essential for mammalian normal development. H3K27 di-methylation (H3K27me2) and H3K27 tri-methylation (H3K27me3) are marks of facultative heterochromatin which maintains transcriptional repression established during early development in many eukaryotes. However, the mechanism underlying establishment and regulation of epigenetic asymmetry in the zygote remains obscure. Here we show that maternal EZH2 is required for the establishment of H3K27me3 in mouse zygotes. However, combined immunostaining with ULI-NChIP-seq (ultra-low-input micrococcal nuclease-based native ChIP-seq) shows that EZH1 could partially safeguard the role of EZH2 in the formation of H3K27me2. Meanwhile, we identify that EHMT1 is involved in the establishment of H3K27me2, and that H3K27me2 might be an essential prerequisite for the following de novo H3K27me3 modification on the male pronucleus. In this work, we clarify the establishment and regulatory mechanisms of H3K27me2 and H3K27me3 in mouse zygotes. Dynamic arrangement of epigenetic modifications such as repressive H3K27 methylation is essential for zygote development. Here the authors show that establishment of genome-wide H3K27me3 in zygotes requires EZH2, that EZH1 partially compensates for EZH2 loss, and that EHMT1 is involved in H3K27me2 establishment.