SUMO modification system facilitates the exchange of histone variant H2A.Z-2 at DNA damage sites

Nucleus. 2018 Jan 1;9(1):87-94. doi: 10.1080/19491034.2017.1395543. Epub 2017 Dec 14.

Abstract

Histone exchange and histone post-translational modifications play important roles in the regulation of DNA metabolism, by re-organizing the chromatin configuration. We previously demonstrated that the histone variant H2A.Z-2 is rapidly exchanged at damaged sites after DNA double strand break induction in human cells. In yeast, the small ubiquitin-like modifier (SUMO) modification of H2A.Z is involved in the DNA damage response. However, whether the SUMO modification regulates the exchange of human H2A.Z-2 at DNA damage sites remains unclear. Here, we show that H2A.Z-2 is SUMOylated in a damage-dependent manner, and the SUMOylation of H2A.Z-2 is suppressed by the depletion of the SUMO E3 ligase, PIAS4. Moreover, PIAS4 depletion represses the incorporation and eviction of H2A.Z-2 at damaged sites. These findings demonstrate that the PIAS4-mediated SUMOylation regulates the exchange of H2A.Z-2 at DNA damage sites.

Keywords: DNA damage; H2A.Z-2; PIAS4; SUMO; histone variant.

MeSH terms

  • DNA / chemistry
  • DNA / metabolism*
  • DNA Damage*
  • HeLa Cells
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Protein Processing, Post-Translational
  • SUMO-1 Protein / metabolism*

Substances

  • Histones
  • SUMO-1 Protein
  • DNA

Grant support

This research was supported by JSPS KAKENHI Grants, number JP26430114 to J.S., number JP25116009 to M.H. and numbers JP16H01312 and JP15H02821 to S.T. This work was partially supported by the Program of the network-type joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University, and Fukushima Medical University