title: Maternal Sall4 Is Indispensable for Epigenetic Maturation of Mouse Oocytes.
abstract: Sall4 (Splat-like 4) plays important roles in maintaining pluripotency of embryonic stem cells and in various developmental processes. Here, we find that Sall4 is highly expressed in oocytes and early embryos. To investigate the roles of SALL4 in oogenesis, we generated Sall4 maternal specific knock-out mice by using CRISPR/Cas9 system, and we find that the maternal deletion of Sall4 causes developmental arrest of oocytes at germinal vesicle stage with non-surrounded nucleus, and the subsequent meiosis resumption is prohibited. We further discover that the loss of maternal Sall4 causes failure in establishment of DNA methylation in oocytes. Furthermore, we find that Sall4 modulates H3K4me3 and H3K27me3 modifications by regulating the expression of key histone demethylases coding genes Kdm5b, Kdm6a, and Kdm6b in oocytes. Moreover, we demonstrate that the aberrant H3K4me3 and H3K27me3 cause mis-expression of genes that are critical for oocytes maturation and meiosis resumption. Taken together, our study explores a pivotal role of Sall4 in regulating epigenetic maturation of mouse oocytes.
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: the Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: the State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: He
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Wang
authors.affiliation: the State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: the State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Baodong
authors.initials: B
authors.lastname: Liu
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Liu
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Kou
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhao
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Hou
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: the State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Wang
authors.affiliation: the State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: the Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hengyu
authors.initials: H
authors.lastname: Fan
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Wang
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: chenjiayu@tongji.edu.cn.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: gaoshaorong@tongji.edu.cn.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D056466:Histone Demethylases / Q000096:biosynthesis / Q000235:genetics; D056484:Jumonji Domain-Containing Histone Demethylases / Q000096:biosynthesis / Q000235:genetics; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C509167:Sall4 protein, mouse; D014157:Transcription Factors; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C485614:Kdm5b protein, mouse; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse
keywords: DNA methylation; embryo; histone methylation; meiosis; oocyte