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Histone methyltransferase SETD2 is required for meiotic maturation in mouse oocyte
Authors:Chunling Li  Feiyang Diao  Danhong Qiu  Manxi Jiang  Xiaoyan Li  Longsen Han  Ling Li  Xiaojing Hou  Juan Ge  Xianghong Ou  Jiayin Liu  Qiang Wang
Institution:1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China;2. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China;3. Fertility Preservation Laboratory, Human Reproduction Medical Center, Guangdong Second Provincial General Hospital, Guangzhou, China;4. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, China

Abstract:SET-domain-containing 2 (SETD2), a member of the histone lysine methyltransferase family, has been reported to be involved in multiple biological processes. However, the function of SETD2 during oocyte maturation has not been addressed. In this study, we find that mouse oocytes are incapable of progressing through meiosis completely once SETD2 is specifically depleted. These oocytes present an abnormal spindle morphology and deficient chromosome movement, with disrupted kinetochore–microtubule attachments, consequently producing aneuploidy eggs. In line with this, the BubR1 signal is markedly elevated in metaphase kinetochores of oocytes with SETD2 depletion, indicative of the activation of spindle assembly checkpoint. In addition, we note that loss of SETD2 results in a drastic decrease in the trimethylation level of H3K36 in oocytes. Collectively, our data demonstrate that SETD2 is required for oocyte maturation and indicate a novel mechanism controlling the meiotic apparatus.
Keywords:histone methylation  meiosis  oocyte  SETD2  spindle
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