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JMJD5 cleaves monomethylated histone H3 N‐tail under DNA damaging stress
Author(s) -
Shen Jing,
Xiang Xueping,
Chen Lihan,
Wang Haiyi,
Wu Li,
Sun Yanyun,
Ma Li,
Gu Xiuting,
Liu Hong,
Wang Lishun,
Yu Yingnian,
Shao Jimin,
Huang Chao,
Chin Y Eugene
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201743892
Subject(s) - histone , genetics , histone h3 , dna , dna damage , biology , microbiology and biotechnology
The histone H3 N‐terminal protein domain (N‐tail) is regulated by multiple posttranslational modifications, including methylation, acetylation, phosphorylation, and by proteolytic cleavage. However, the mechanism underlying H3 N‐tail proteolytic cleavage is largely elusive. Here, we report that JMJD 5, a Jumonji C (JmjC) domain‐containing protein, is a Cathepsin L‐type protease that mediates histone H3 N‐tail proteolytic cleavage under stress conditions that cause a DNA damage response. JMJD 5 clips the H3 N‐tail at the carboxyl side of monomethyl‐lysine (Kme1) residues. In vitro H3 peptide digestion reveals that JMJD 5 exclusively cleaves Kme1 H3 peptides, while little or no cleavage effect of JMJD 5 on dimethyl‐lysine (Kme2), trimethyl‐lysine (Kme3), or unmethyl‐lysine (Kme0) H3 peptides is observed. Although H3 Kme1 peptides of K4, K9, K27, and K36 can all be cleaved by JMJD 5 in vitro , K9 of H3 is the major cleavage site in vivo , and H3.3 is the major H3 target of JMJD 5 cleavage. Cleavage is enhanced at gene promoters bound and repressed by JMJD 5 suggesting a role for H3 N‐tail cleavage in gene expression regulation.