JMJD5 cleaves monomethylated histone H3 N-tail under DNA damaging stress.

Abstract:

: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 JMJD5, 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. JMJD5 clips the H3 N-tail at the carboxyl side of monomethyl-lysine (Kme1) residues. In vitro H3 peptide digestion reveals that JMJD5 exclusively cleaves Kme1 H3 peptides, while little or no cleavage effect of JMJD5 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 JMJD5 in vitro, K9 of H3 is the major cleavage site in vivo, and H3.3 is the major H3 target of JMJD5 cleavage. Cleavage is enhanced at gene promoters bound and repressed by JMJD5 suggesting a role for H3 N-tail cleavage in gene expression regulation.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Shen J,Xiang X,Chen L,Wang H,Wu L,Sun Y,Ma L,Gu X,Liu H,Wang L,Yu YN,Shao J,Huang C,Chin YE

doi

10.15252/embr.201743892

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

2131-2143

issue

12

eissn

1469-221X

issn

1469-3178

pii

embr.201743892

journal_volume

18

pub_type

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