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Cell Rep. 2019 Apr 2;27(1):282-293.e4. doi: 10.1016/j.celrep.2019.03.002.

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

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Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Department of Medical Genetics, Life Sciences Institute, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Faculty of Biology-Oriented Science and Technology, KINDAI University, Wakayama 649-6493, Japan.
Institute of Molecular Genetics of Montpellier, CNRS, University of Montpellier, 34293 Montpellier, France.
Laboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
Cellular Memory Laboratory, Cluster for Pioneering Research, RIKEN, Wako, Saitama 351-0198, Japan.
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. Electronic address:


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.


DNA methylation; G9a; H3K9me2; chromatin organization; chromosome segregation; histone modification; oocyte; preimplantation embryo

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