第 596 回生医研セミナー(多階層生体防御システム研究拠点)
グローバルCOE理医連携セミナー
ゲノミクスエピゲノミクス研究拠点セミナー

この度、中国科学院上海生命科学研究院の徐国良(Guoliang Xu)先生に生体防御医学研究所でのセミナーをお願い致しました。このセミナーでは、マウス受精胚ゲノムにおける5-メチルシトシンの水酸化が、多能性遺伝子の活性化や移植体細胞核のリプログラミングに重要な役割を果たすことについてお話しいただきます。その成果は2つのhigh impact journalに最近掲載されています。講演は英語で行われます。ご来聴を歓迎致します。

演題DNA oxidation towards totipotency in mammalian development.
(seminar in English)

演者徐 国良 先生
中国科学院生命科学研究院 教授

Prof. Guoliang Xu
Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai

日時平成23年11月29日(火)15時半より16時半まで
Nov. 29, 2011(Tue), 15:30-16:30

場所馬出医学系キャンパス内 生体防御医学研究所 本館1階会議室
以下の地図の21番になります。
http://www.kyushu-u.ac.jp/access/map/hospital/hospital.html

Medical Institute of Bioregulation, Main Building 1F, Seminar Room
No.21 on the following linked map
http://www.kyushu-u.ac.jp/access/map/hospital/hospital-e.html

要旨 Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming following fertilization. The paternal genome undergoes active DNA demethylation before the first mitotic division. The biological significance and mechanisms of paternal epigenome remodeling have remained unclear. We find that, within mouse zygotes, oxidation of occurs in the paternal genome, changing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). In Tet3-deficient zygotes from conditional knockout mice, the conversion of 5mC into 5hmC fails to occur. Thus, the loss of 5mC in the paternal genome in zygotes is caused by its conversion to 5hmC mediated by Tet3. Deficiency of Tet3 also impedes demethylation at the paternal copy of genes such as Oct4 and Nanog and delays the subsequent reactivation of Oct4 in early embryos. Heterozygous mutant embryos lacking maternal Tet3 suffer increased developmental failures, with female mice depleted of Tet3 in the germ line displaying severely reduced fecundity. Importantly, oocytes lacking Tet3 also show impaired reprogramming of injected somatic cell nuclei. We conclude that Tet3-mediated DNA oxidation is essential for epigenetic reprogramming in the early embryo following natural fertilization, as well as for the reprogramming of somatic cell nuclei during animal cloning.

業績
  1. Tian-Peng Gu, et al.
    The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477: 606-610, 2011.
  2. Yu-Fei He, et al.
    Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333: 1303–1307, 2011.

連絡先生体防御医学研究所 エピゲノム学分野 佐々木 裕之
Division of Epigenomics, MIB, Hiroyuki SASAKI
電話:092-642-6759


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