Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse.
Oocyte meiotic progression and maternal-to-zygote transition are accompanied by dynamic epigenetic changes. The functional significance of these changes and the key epigenetic regulators involved are largely unknown. Here we show that Setdb1, a lysine methyltransferase, controls the global level of...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-04-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4829257?pdf=render |
| _version_ | 1828364817417633792 |
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| author | Jeesun Kim Hongbo Zhao Jiameng Dan Soojin Kim Swanand Hardikar Debra Hollowell Kevin Lin Yue Lu Yoko Takata Jianjun Shen Taiping Chen |
| author_facet | Jeesun Kim Hongbo Zhao Jiameng Dan Soojin Kim Swanand Hardikar Debra Hollowell Kevin Lin Yue Lu Yoko Takata Jianjun Shen Taiping Chen |
| author_sort | Jeesun Kim |
| collection | DOAJ |
| description | Oocyte meiotic progression and maternal-to-zygote transition are accompanied by dynamic epigenetic changes. The functional significance of these changes and the key epigenetic regulators involved are largely unknown. Here we show that Setdb1, a lysine methyltransferase, controls the global level of histone H3 lysine 9 di-methyl (H3K9me2) mark in growing oocytes. Conditional deletion of Setdb1 in developing oocytes leads to meiotic arrest at the germinal vesicle and meiosis I stages, resulting in substantially fewer mature eggs. Embryos derived from these eggs exhibit severe defects in cell cycle progression, progressive delays in preimplantation development, and degeneration before reaching the blastocyst stage. Rescue experiments by expressing wild-type or inactive Setdb1 in Setdb1-deficient oocytes suggest that the catalytic activity of Setdb1 is essential for meiotic progression and early embryogenesis. Mechanistically, up-regulation of Cdc14b, a dual-specificity phosphatase that inhibits meiotic progression, greatly contributes to the meiotic arrest phenotype. Setdb1 deficiency also leads to derepression of transposons and increased DNA damage in oocytes, which likely also contribute to meiotic defects. Thus, Setdb1 is a maternal-effect gene that controls meiotic progression and is essential for early embryogenesis. Our results uncover an important link between the epigenetic machinery and the major signaling pathway governing meiotic progression. |
| first_indexed | 2024-04-14T05:21:21Z |
| format | Article |
| id | doaj.art-46377a802a1345aab117ae38590d51ff |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-14T05:21:21Z |
| publishDate | 2016-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-46377a802a1345aab117ae38590d51ff2022-12-22T02:10:09ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-04-01124e100597010.1371/journal.pgen.1005970Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse.Jeesun KimHongbo ZhaoJiameng DanSoojin KimSwanand HardikarDebra HollowellKevin LinYue LuYoko TakataJianjun ShenTaiping ChenOocyte meiotic progression and maternal-to-zygote transition are accompanied by dynamic epigenetic changes. The functional significance of these changes and the key epigenetic regulators involved are largely unknown. Here we show that Setdb1, a lysine methyltransferase, controls the global level of histone H3 lysine 9 di-methyl (H3K9me2) mark in growing oocytes. Conditional deletion of Setdb1 in developing oocytes leads to meiotic arrest at the germinal vesicle and meiosis I stages, resulting in substantially fewer mature eggs. Embryos derived from these eggs exhibit severe defects in cell cycle progression, progressive delays in preimplantation development, and degeneration before reaching the blastocyst stage. Rescue experiments by expressing wild-type or inactive Setdb1 in Setdb1-deficient oocytes suggest that the catalytic activity of Setdb1 is essential for meiotic progression and early embryogenesis. Mechanistically, up-regulation of Cdc14b, a dual-specificity phosphatase that inhibits meiotic progression, greatly contributes to the meiotic arrest phenotype. Setdb1 deficiency also leads to derepression of transposons and increased DNA damage in oocytes, which likely also contribute to meiotic defects. Thus, Setdb1 is a maternal-effect gene that controls meiotic progression and is essential for early embryogenesis. Our results uncover an important link between the epigenetic machinery and the major signaling pathway governing meiotic progression.http://europepmc.org/articles/PMC4829257?pdf=render |
| spellingShingle | Jeesun Kim Hongbo Zhao Jiameng Dan Soojin Kim Swanand Hardikar Debra Hollowell Kevin Lin Yue Lu Yoko Takata Jianjun Shen Taiping Chen Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. PLoS Genetics |
| title | Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. |
| title_full | Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. |
| title_fullStr | Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. |
| title_full_unstemmed | Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. |
| title_short | Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. |
| title_sort | maternal setdb1 is required for meiotic progression and preimplantation development in mouse |
| url | http://europepmc.org/articles/PMC4829257?pdf=render |
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