Open AccessUsp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
Author(s) -
Luna Yamaguchi,
Atsuya Nishiyama,
Toshinori Misaki,
Yoshikazu Johmura,
Junji Ueda,
Kyohei Arita,
Koji Nagao,
Chikashi Obuse,
Makoto Nakanishi
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-00136-5
Subject(s) - histone methyltransferase , dna methylation , histone h2a , epigenomics , histone methylation , dnmt1 , cancer epigenetics , histone , histone code , biology , chromatin , epigenetics , eukaryotic dna replication , microbiology and biotechnology , dna methyltransferase , dna replication , dna , chemistry , methylation , biochemistry , methyltransferase , nucleosome , gene expression , gene
Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro . Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA methylation.