UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications

被引：101

作者：

Hashimoto, Hideharu ^{[1
]}

Horton, John R. ^{[1
]}

Zhang, Xing ^{[1
]}

Cheng, Xiaodong ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

来源：

EPIGENETICS | 2009年 / 4卷 / 01期

基金：

美国国家卫生研究院;

关键词：

DNA methylation; histone modifications; base flipping; SRA domain; inter-domain interactions; SRA DOMAIN; LINEAR DIFFUSION; STRUCTURAL BASIS; BINDING; RECOGNITION; BASE; NP95; METHYLTRANSFERASE; MECHANISM; COMPLEX;

D O I：

10.4161/epi.4.1.7370

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：

Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication.

引用

页码：8 / 14

页数：7

共 4 条

[1] The histone and non-histone methyllysine reader activities of the UHRF1 tandem Tudor domain are dispensable for the propagation of aberrant DNA methylation patterning in cancer cells
Vaughan, Robert M.
Kupai, Ariana
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Tiedemann, Rochelle L.
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Shaw, Kevin M.
Krajewski, Krzysztof
Strahl, Brian D.
Bedford, Mark T.
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Dickson, Bradley M.
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EPIGENETICS & CHROMATIN, 2020, 13 (01)
[2] The multi-domain protein Np95 connects DNA methylation and histone modification
Rottach, Andrea
Frauer, Carina
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Bonapace, Ian Marc
Spada, Fabio
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NUCLEIC ACIDS RESEARCH, 2010, 38 (06) : 1796 - 1804
[3] Dual Functions of the RFTS Domain of Dnmt1 in Replication-Coupled DNA Methylation and in Protection of the Genome from Aberrant Methylation
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Hasegawa, Takashi
Kimura, Hironobu
Sharif, Jafar
Muto, Masahiro
Koseki, Haruhiko
Takahashi, Saori
Suetake, Isao
Tajima, Shoji
PLOS ONE, 2015, 10 (09):
[4] Drug discovery targeting epigenetic codes: The great potential of UHRF1, which links DNA methylation and histone modifications, as a drug target in cancers and toxoplasmosis
Unoki, Motoko
Brunet, Julie
Mousli, Marc
BIOCHEMICAL PHARMACOLOGY, 2009, 78 (10) : 1279 - 1288

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