Histone H3K9 Methyltransferase G9a in Oocytes Is Essential for Preimplantation Development but Dispensable for CG Methylation Protection

Summary: Mammalian histone methyltransferase G9a (also called EHMT2) deposits H3K9me2 on chromatin and is essential for postimplantation development. However, its role in oogenesis and preimplantation development remains poorly understood. We show that H3K9me2-enriched chromatin domains in mouse oocytes are generally depleted of CG methylation, contrasting with their association in embryonic stem and somatic cells. Oocyte-specific disruption of G9a results in reduced H3K9me2 enrichment and impaired reorganization of heterochromatin in oocytes, but only a modest reduction in CG methylation is detected. Furthermore, in both oocytes and 2-cell embryos, G9a depletion has limited impact on the expression of genes and retrotransposons. Although their CG methylation is minimally affected, preimplantation embryos derived from such oocytes show abnormal chromosome segregation and frequent developmental arrest. Our findings illuminate the functional importance of G9a independent of CG methylation in preimplantation development and call into question the proposed role for H3K9me2 in CG methylation protection in zygotes. : Au Yeung et al. report that H3K9 methyltransferase G9a in mouse oocytes is essential for preimplantation development. Contrary to the previous model, however, maternal G9a is dispensable for CG methylation protection in zygotes and is instead important for chromatin reorganization in oocytes and proper chromosome segregation in preimplantation embryos. Keywords: oocyte, preimplantation embryo, histone modification, DNA methylation, G9a, H3K9me2, chromatin organization, chromosome segregatio

Additional file 1 of DPPA3 facilitates genome-wide DNA demethylation in mouse primordial germ cells

Additional file 1: Fig. S1. Dppa3 KO in mouse PGCs. Related to Fig. 1. Fig. S2. CG methylation in oocytes [61, 62]. Related to Fig. 2. Fig. S3. Reprogramming defects persists in postnatal oocytes. Related to Fig. 3. Fig. S4. DPPA3 acts in the downstream of PRDM14 and independent of TET1. Related to Fig. 4. Table S1. Number of PGCs collected in this study. Related to Fig. 1 and Fig. S1. Table S2. Sequencing and mapping summary of WGBS. Related to Fig. 1 and Fig. S1. Table S3. Sequencing and mapping summary of RNA-seq. Related to Fig. S3. Table S4. Downregulated transcripts in maternal KO 2-cell embryos which are persistently hypermethylated in KO PGCs and KO FGOs. Related to Fig. S