論文

査読有り 筆頭著者 責任著者
2013年10月

Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication

NATURE
  • Atsuya Nishiyama
  • Luna Yamaguchi
  • Jafar Sharif
  • Yoshikazu Johmura
  • Takeshi Kawamura
  • Keiko Nakanishi
  • Shintaro Shimamura
  • Kyohei Arita
  • Tatsuhiko Kodama
  • Fuyuki Ishikawa
  • Haruhiko Koseki
  • Makoto Nakanishi
  • 全て表示

502
7470
開始ページ
249
終了ページ
+
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/nature12488
出版者・発行元
NATURE PUBLISHING GROUP

Faithful propagation of DNA methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells(1-5). Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA methylation by recruiting Dnmt1 to hemi-methylated DNA sites(6-10), the mechanism by which Uhrf1 coordinates the maintenance of DNA methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence(11). The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA methylation and DNA replication through histone H3 ubiquitylation.

リンク情報
DOI
https://doi.org/10.1038/nature12488
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24013172
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000325436100054&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-84885577142&partnerID=MN8TOARS
URL
http://orcid.org/0000-0002-8416-3776
ID情報
  • DOI : 10.1038/nature12488
  • ISSN : 0028-0836
  • eISSN : 1476-4687
  • ORCIDのPut Code : 30857520
  • PubMed ID : 24013172
  • SCOPUS ID : 84885577142
  • Web of Science ID : WOS:000325436100054

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