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. 2020 Jan;25(1):22-32.
doi: 10.1111/gtc.12732. Epub 2019 Dec 3.

Enhanced processivity of Dnmt1 by monoubiquitinated histone H3

Yuichi Mishima  1 , Laura Brueckner  1 , Saori Takahashi  1 , Toru Kawakami  2 , Junji Otani  1 , Akira Shinohara  3 , Kohei Takeshita  4 , Ronald Garingalao Garvilles  1 , Mikio Watanabe  5 , Norio Sakai  5 , Hideyuki Takeshima  6 , Charlotte Nachtegael  1   7 , Atsuya Nishiyama  8 , Makoto Nakanishi  8 , Kyohei Arita  9 , Kinichi Nakashima  10 , Hironobu Hojo  2 , Isao Suetake  1   5   11
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Free article

Enhanced processivity of Dnmt1 by monoubiquitinated histone H3

Yuichi Mishima et al. Genes Cells. 2020 Jan.
Free article

Abstract

DNA methylation controls gene expression, and once established, DNA methylation patterns are faithfully copied during DNA replication by the maintenance DNA methyltransferase Dnmt1. In vivo, Dnmt1 interacts with Uhrf1, which recognizes hemimethylated CpGs. Recently, we reported that Uhrf1-catalyzed K18- and K23-ubiquitinated histone H3 binds to the N-terminal region (the replication focus targeting sequence, RFTS) of Dnmt1 to stimulate its methyltransferase activity. However, it is not yet fully understood how ubiquitinated histone H3 stimulates Dnmt1 activity. Here, we show that monoubiquitinated histone H3 stimulates Dnmt1 activity toward DNA with multiple hemimethylated CpGs but not toward DNA with only a single hemimethylated CpG, suggesting an influence of ubiquitination on the processivity of Dnmt1. The Dnmt1 activity stimulated by monoubiquitinated histone H3 was additively enhanced by the Uhrf1 SRA domain, which also binds to RFTS. Thus, Dnmt1 activity is regulated by catalysis (ubiquitination)-dependent and -independent functions of Uhrf1.

Keywords: Dnmt1; RFTS; SRA; methylation; processivity; ubiquitinated histone.

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References

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