Repository logo
 

Citrullination of HP1γ chromodomain affects association with chromatin.

Accepted version
Peer-reviewed

Change log

Authors

Wiese, Meike 
Bannister, Andrew J 
Basu, Srinjan 
Boucher, Wayne 
Wohlfahrt, Kai 

Abstract

BACKGROUND: Stem cell differentiation involves major chromatin reorganisation, heterochromatin formation and genomic relocalisation of structural proteins, including heterochromatin protein 1 gamma (HP1γ). As the principal reader of the repressive histone marks H3K9me2/3, HP1 plays a key role in numerous processes including heterochromatin formation and maintenance. RESULTS: We find that HP1γ is citrullinated in mouse embryonic stem cells (mESCs) and this diminishes when cells differentiate, indicating that it is a dynamically regulated post-translational modification during stem cell differentiation. Peptidylarginine deiminase 4, a known regulator of pluripotency, citrullinates HP1γ in vitro. This requires R38 and R39 within the HP1γ chromodomain, and the catalytic activity is enhanced by trimethylated H3K9 (H3K9me3) peptides. Mutation of R38 and R39, designed to mimic citrullination, affects HP1γ binding to H3K9me3-containing peptides. Using live-cell single-particle tracking, we demonstrate that R38 and R39 are important for HP1γ binding to chromatin in vivo. Furthermore, their mutation reduces the residence time of HP1γ on chromatin in differentiating mESCs. CONCLUSION: Citrullination is a novel post-translational modification of the structural heterochromatin protein HP1γ in mESCs that is dynamically regulated during mESC differentiation. The citrullinated residues lie within the HP1γ chromodomain and are important for H3K9me3 binding in vitro and chromatin association in vivo.

Description

Keywords

Chromatin, Citrullination, Stem cell differentiation, Animals, Binding Sites, Cell Differentiation, Cell Line, Chromosomal Proteins, Non-Histone, Citrullination, Heterochromatin, Histone Code, Histones, Mice, Mouse Embryonic Stem Cells, Mutation, Protein Binding, Protein-Arginine Deiminases

Journal Title

Epigenetics Chromatin

Conference Name

Journal ISSN

1756-8935
1756-8935

Volume Title

12

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (17001)
Medical Research Council (MR/M010082/1)
Medical Research Council (MR/P019471/1)
Wellcome Trust (206291/Z/17/Z)
European Commission (277899)
Cancer Research UK (C7/A18061)
Medical Research Council (MR/K015850/1)
Cancer Research UK (C6946/A24843)
Wellcome Trust (203144/Z/16/Z)
Medical Research Council (MC_PC_12009)
Cancer Research UK (grant reference RG17001) Wellcome Trust (Core Grant reference WT203144) Cancer Research UK (grant reference C6946/A24843). Wellcome Trust (206291/Z/17/Z) Medical Research Council (MR/P019471/1 and MR/M010082/1). Royal Society Professorship (RP150066) Medical Research Council (MR/K015850/1)