Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development |
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| Authors: | Keisuke Aoshima Erina Inoue Hirofumi Sawa Yuki Okada |
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| Institution: | 1. Laboratory of Pathology and Development, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo‐ku, Tokyo, Japan;2. Division of Molecular Pathobiology, Center for Zoonosis Control, Hokkaido University, Kita‐ku, Sapporo, Japan;3. Research Fellow of Japan Society for the Promotion of Science, Chiyoda‐ku, Tokyo, Japan;4. PRESTO, Japan Science and Technology Agency (JST), Kawaguchi‐Honcho, Saitama, Japan |
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| Abstract: | Epigenetic modifications, such as DNA methylation and histone modifications, are dynamically altered predominantly in paternal pronuclei soon after fertilization. To identify which histone modifications are required for early embryonic development, we utilized histone K‐M mutants, which prevent endogenous histone methylation at the mutated site. We prepared four single K‐M mutants for histone H3.3, K4M, K9M, K27M, and K36M, and demonstrate that overexpression of H3.3 K4M in embryos before fertilization results in developmental arrest, whereas overexpression after fertilization does not affect the development. Furthermore, loss of H3K4 methylation decreases the level of minor zygotic gene activation (ZGA) predominantly in the paternal pronucleus, and we obtained similar results from knockdown of the H3K4 methyltransferase Mll3/4. We therefore conclude that H3K4 methylation, likely established by Mll3/4 at the early pronuclear stage, is essential for the onset of minor ZGA in the paternal pronucleus, which is necessary for subsequent preimplantation development in mice. |
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| Keywords: | histone methylation K‐M mutant minor ZGA Mll3/4 |
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