RFTS-dependent negative regulation of Dnmt1 by nucleosome structure and histone tails.

Yuichi Mishima, Laura Brueckner, Saori Takahashi, Toru Kawakami, Kyohei Arita, Shota Oka, Junji Otani, Hironobu Hojo, Masahiro Shirakawa, Akira Shinohara, Mikio Watanabe, Isao Suetake

The FEBS journal 2017 Oct

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DNA methylation in promoter regions represses gene expression and is copied over mitotic divisions by Dnmt1. Dnmt1 activity is regulated by its replication foci targeting sequence (RFTS) domain which masks the catalytic pocket. It has been shown that Dnmt1 activity on unmethylated DNA is inhibited in nucleosome cores. In the present study, we aimed to assess the effect of nuclesome formation on maintenance methylation at single CpG resolution. We show that Dnmt1 fully methylates naked linker DNA in dinucleosomes, whereas maintenance methylation was repressed at all CpG sites in nucleosome core particles. Deletion of RFTS partly released obstruction of Dnmt1 activity in core particles. Histone H3 tail peptides inhibited Dnmt1 in an RFTS-dependent manner and repression was modulated by acetylation or methylation. We propose a novel function of RFTS to regulate Dnmt1 activity in nucleosomes. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Citation

Yuichi Mishima, Laura Brueckner, Saori Takahashi, Toru Kawakami, Kyohei Arita, Shota Oka, Junji Otani, Hironobu Hojo, Masahiro Shirakawa, Akira Shinohara, Mikio Watanabe, Isao Suetake. RFTS-dependent negative regulation of Dnmt1 by nucleosome structure and histone tails. The FEBS journal. 2017 Oct;284(20):3455-3469