SRA

Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryogenesis. Here we show that H3K9me2 directs repression of 2-cell stage specific genes in nascent embryos to facilitate preimplantation development. Thereafter, genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with redistribution of EZH2-dependent histone H3 lysine 27 trimethylation (H3K27me3). Loss of G9a or EZH2 results in upregulation of distinct gene sets involved in processes such as cell cycle regulation as well as germline and embryonic development. Accumulation of H3K9me2 not only occurs at promoters and gene bodies, but also extends to active enhancer elements to promote their developmentally-linked silencing. This epigenetic mechanism is important for priming gene regulatory networks in epiblast cells undergoing rapid cell proliferation in preparation for critical cell fate decisions. Overall design: Examination of 2 histone modification in 3 cell types and transcriptional analysis of G9a and Ezh2 KO epiblasts and Whole genome bisulfite sequencing in two cell types