論文

査読有り 国際誌
2020年3月6日

Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation.

Nature communications
  • Atsuya Nishiyama
  • Christopher B Mulholland
  • Sebastian Bultmann
  • Satomi Kori
  • Akinori Endo
  • Yasushi Saeki
  • Weihua Qin
  • Carina Trummer
  • Yoshie Chiba
  • Haruka Yokoyama
  • Soichiro Kumamoto
  • Toru Kawakami
  • Hironobu Hojo
  • Genta Nagae
  • Hiroyuki Aburatani
  • Keiji Tanaka
  • Kyohei Arita
  • Heinrich Leonhardt
  • Makoto Nakanishi
  • 全て表示

11
1
開始ページ
1222
終了ページ
1222
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-020-15006-4

Stable inheritance of DNA methylation is critical for maintaining differentiated phenotypes in multicellular organisms. We have recently identified dual mono-ubiquitylation of histone H3 (H3Ub2) by UHRF1 as an essential mechanism to recruit DNMT1 to chromatin. Here, we show that PCNA-associated factor 15 (PAF15) undergoes UHRF1-dependent dual mono-ubiquitylation (PAF15Ub2) on chromatin in a DNA replication-coupled manner. This event will, in turn, recruit DNMT1. During early S-phase, UHRF1 preferentially ubiquitylates PAF15, whereas H3Ub2 predominates during late S-phase. H3Ub2 is enhanced under PAF15 compromised conditions, suggesting that H3Ub2 serves as a backup for PAF15Ub2. In mouse ES cells, loss of PAF15Ub2 results in DNA hypomethylation at early replicating domains. Together, our results suggest that there are two distinct mechanisms underlying replication timing-dependent recruitment of DNMT1 through PAF15Ub2 and H3Ub2, both of which are prerequisite for high fidelity DNA methylation inheritance.

リンク情報
DOI
https://doi.org/10.1038/s41467-020-15006-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32144273
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060239
ID情報
  • DOI : 10.1038/s41467-020-15006-4
  • PubMed ID : 32144273
  • PubMed Central 記事ID : PMC7060239

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