MSK-Mediated Phosphorylation of Histone H3 Ser28 Couples MAPK Signalling with Early Gene Induction and Cardiac Hypertrophy

Emma L. Robinson (Lead / Corresponding author), Faye M. Drawnel, Saher Mehdi, Caroline R. Archer, Wei Liu, Hanneke Okkenhaug, Kanar Alkass, Jan Magnus Aronsen, Chandan K. Nagaraju, Ivar Sjaastad, Karin R. Sipido, Olaf Bergmann, J. Simon C. Arthur, Xin Wang, H. Llewelyn Roderick (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
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Abstract

Heart failure is a leading cause of death that develops subsequent to deleterious hyper-trophic cardiac remodelling. MAPK pathways play a key role in coordinating the induction of gene expression during hypertrophy. Induction of the immediate early gene (IEG) response including activator protein 1 (AP-1) complex factors is a necessary and early event in this process. How MAPK and IEG expression are coupled during cardiac hypertrophy is not resolved. Here, in vitro, in rodent models and in human samples, we demonstrate that MAPK-stimulated IEG induction depends on the mitogen and stress-activated protein kinase (MSK) and its phosphorylation of histone H3 at serine 28 (pH3S28). pH3S28 in IEG promoters in turn recruits Brg1, a BAF60 ATP-dependent chromatin remodelling complex component, initiating gene expression. Without MSK activity and IEG induction, the hypertrophic response is suppressed. These studies provide new mechanistic insights into the role of MAPK pathways in signalling to the epigenome and regulation of gene expression during cardiac hypertrophy.

Original languageEnglish
Article number604
Pages (from-to)1-27
Number of pages27
JournalCells
Volume11
Issue number4
DOIs
Publication statusPublished - 9 Feb 2022

Keywords

  • Cardiomyocyte
  • Hypertrophy
  • Immediate early genes
  • MSK
  • Phosphorylated histone 3 serine 28

ASJC Scopus subject areas

  • General Medicine

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