Apoptotic phosphorylation of histone H3 on Ser-10 by protein kinase Cδ

PLoS One. 2012;7(9):e44307. doi: 10.1371/journal.pone.0044307. Epub 2012 Sep 12.

Abstract

Phosphorylation of histone H3 on Ser-10 is regarded as an epigenetic mitotic marker and is tightly correlated with chromosome condensation during both mitosis and meiosis. However, it was also reported that histone H3 Ser-10 phosphorylation occurs when cells are exposed to various death stimuli, suggesting a potential role in the regulation of apoptosis. Here we report that histone H3 Ser-10 phosphorylation is mediated by the pro-apoptotic kinase protein kinase C (PKC) δ during apoptosis. We observed that PKCδ robustly phosphorylates histone H3 on Ser-10 both in vitro and in vivo. Ectopic expression of catalytically active PKCδ efficiently induces condensed chromatin structure in the nucleus. We also discovered that activation of PKCδ is required for histone H3 Ser-10 phosphorylation after treatment with DNA damaging agents during apoptosis. Collectively, these findings suggest that PKCδ is the kinase responsible for histone H3 Ser-10 phosphoryation during apoptosis and thus contributes to chromatin condensation together with other apoptosis-related histone modifications. As a result, histone H3 Ser-10 phosphorylation can be designated a new 'apoptotic histone code' mediated by PKCδ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Biocatalysis
  • Cell Line
  • Chromatin / metabolism
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Models, Biological
  • Phosphorylation
  • Phosphoserine / metabolism*
  • Protein Kinase C-delta / metabolism*

Substances

  • Chromatin
  • Histones
  • Phosphoserine
  • Protein Kinase C-delta

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) (No. 20110027957, 20110031234, 20120005830, and WCU program R31–10105). This work was also supported by the Brain Korea 21 program and the National Frontier Research Program (20110031517) of the Korean Ministry of Education, Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.