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

被引:7
作者
Mishima, Yuichi [1 ]
Brueckner, Laura [1 ]
Takahashi, Saori [1 ]
Kawakami, Toru [2 ]
Arita, Kyohei [3 ]
Oka, Shota [1 ]
Otani, Junji [1 ]
Hojo, Hironobu [2 ]
Shirakawa, Masahiro [4 ,5 ]
Shinohara, Akira [6 ]
Watanabe, Mikio [7 ]
Suetake, Isao [1 ,5 ,7 ,8 ]
机构
[1] Osaka Univ, Inst Prot Res, Lab Epigenet, Suita, Osaka, Japan
[2] Osaka Univ, Inst Prot Res, Lab Organ Chem, Suita, Osaka, Japan
[3] Yokohama City Univ, Grad Sch Nanobiosci, Div Macromol Crystallog, Yokohama, Kanagawa, Japan
[4] Kyoto Univ, Grad Sch Engn, Dept Mol Engn, Kyoto, Japan
[5] Japan Sci & Technol Agcy, CREST, Saitama, Japan
[6] Osaka Univ, Inst Prot Res, Lab Genome Chromosome Funct, Suita, Osaka, Japan
[7] Osaka Univ, Grad Sch Med, Ctr Twin Res, Suita, Osaka, Japan
[8] Koshien Univ, Coll Nutr, Takarazuka, Hyogo, Japan
关键词
Dnmt1; histone; modifications; nucleosomes; replication foci targeting sequence; MAINTENANCE DNA METHYLATION; REPLICATION FOCI; METHYLTRANSFERASE; SITES; CHROMATIN; BINDING; DOMAIN; H3; AUTOINHIBITION; PURIFICATION;
D O I
10.1111/febs.14205
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3455 / 3469
页数:15
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