title: LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice.
abstract: Mammalian oocytes are arrested at prophase I until puberty when hormonal signals induce the resumption of meiosis I and progression to meiosis II. Meiotic progression is controlled by CDK1 activity and is accompanied by dynamic epigenetic changes. Although the signalling pathways regulating CDK1 activity are well defined, the functional significance of epigenetic changes remains largely unknown. Here we show that LSD1, a lysine demethylase, regulates histone H3 lysine 4 di-methylation (H3K4me2) in mouse oocytes and is essential for meiotic progression. Conditional deletion of Lsd1 in growing oocytes results in precocious resumption of meiosis and spindle and chromosomal abnormalities. Consequently, most Lsd1-null oocytes fail to complete meiosis I and undergo apoptosis. Mechanistically, upregulation of CDC25B, a phosphatase that activates CDK1, is responsible for precocious meiotic resumption and also contributes to subsequent spindle and chromosomal defects. Our findings uncover a functional link between LSD1 and the major signalling pathway governing meiotic progression.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
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, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
authors.forename: Anup Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
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, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
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, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
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, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Kerenyi
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.|Howard Hughes Medical Institute, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.|Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA.
authors.forename: Taiping
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology*; D015398:Signal Transduction; D015854:Up-Regulation; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000378:metabolism
chemical_list: D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D016203:CDC2 Protein Kinase; C517006:Cdc25b protein, mouse; D020687:cdc25 Phosphatases