title: Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse.
abstract: 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.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Jeesun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Jiameng
authors.initials: J
authors.lastname: Dan
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Soojin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Swanand
authors.initials: S
authors.lastname: Hardikar
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Debra
authors.initials: D
authors.lastname: Hollowell
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takata
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States of America.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States of America.
authors.forename: Taiping
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D002453:Cell Cycle / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D018626:Retroelements / Q000235:genetics
chemical_list: D006657:Histones; D034741:RNA, Small Interfering; D018626:Retroelements; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse; C541950:CDC14B protein, mouse; D054637:Dual-Specificity Phosphatases