TY - JOUR
T1 - Enhanced processivity of Dnmt1 by monoubiquitinated histone H3
AU - Mishima, Yuichi
AU - Brueckner, Laura
AU - Takahashi, Saori
AU - Kawakami, Toru
AU - Otani, Junji
AU - Shinohara, Akira
AU - Takeshita, Kohei
AU - Garvilles, Ronald Garingalao
AU - Watanabe, Mikio
AU - Sakai, Norio
AU - Takeshima, Hideyuki
AU - Nachtegael, Charlotte
AU - Nishiyama, Atsuya
AU - Nakanishi, Makoto
AU - Arita, Kyohei
AU - Nakashima, Kinichi
AU - Hojo, Hironobu
AU - Suetake, Isao
N1 - Funding Information:
Funding information JSPS KAKENHI, Grant/Award Number: 15K14418 and 18K06095; AMED-CREST from the Japan Agency for Medical Research and Development; Collaborative Research Program as the Visiting Fellow of Institute for Protein Research, Osaka University, Grant/Award Number: VFCR-18-04; Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED, Grant/Award Number JP19am0101070. We thank Dr. Shoji Tajima for preparing several expression vectors and for critical discussions. We also acknowledge Ms. Kaori Tada, Keiko Shinohara and Junko Abe for protein purification. This work was performed in part under the Collaborative Research Program as the Visiting Fellow of Institute for Protein Research, Osaka University, VFCR-18-04 (IS) and the Cooperative Research Program of the institute, CR-18-03 (YM).
Funding Information:
We thank Dr. Shoji Tajima for preparing several expression vectors and for critical discussions. We also acknowledge Ms. Kaori Tada, Keiko Shinohara and Junko Abe for protein purification. This work was performed in part under the Collaborative Research Program as the Visiting Fellow of Institute for Protein Research, Osaka University, VFCR‐18‐04 (IS) and the Cooperative Research Program of the institute, CR‐18‐03 (YM).
Publisher Copyright:
© 2019 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
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U2 - 10.1111/gtc.12732
DO - 10.1111/gtc.12732
M3 - Article
C2 - 31680384
AN - SCOPUS:85076104999
VL - 25
SP - 22
EP - 32
JO - Genes to Cells
JF - Genes to Cells
SN - 1356-9597
IS - 1
ER -