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

Research output: Contribution to journalResearch articleContributedpeer-review


  • Emma Robinson - (Author)
  • Faye M. Drawnel - (Author)
  • Saher Mehdi - (Author)
  • Caroline R. Archer - (Author)
  • Wei Liu - , Chair of Physical Chemistry (Author)
  • Hanneke Okkenhaug - (Author)
  • Kanar Alkass - (Author)
  • Jan Magnus Aronsen - (Author)
  • Chandan K. Nagaraju - (Author)
  • Ivar Sjaastad - (Author)
  • Karin Sipido - (Author)
  • Olaf Bergmann - , Dynamics and Mechanisms of Cell Renewal (Junior Research Group) (Author)
  • J. Simon C. Arthur - (Author)
  • Xin Wang - (Author)
  • H Llewelyn Roderick - (Author)


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
Issue number4
Publication statusPublished - 9 Feb 2022

External IDs

Scopus 85124143658
PubMed 35203255
unpaywall 10.3390/cells11040604
Mendeley fa04322a-4a6c-36c6-a323-c559b6b47b2d
WOS 000778156000001



  • Cardiomyocyte, Hypertrophy, Immediate early genes, MSK, Phosphorylated histone 3 serine 28, Gene Expression, Phosphorylation, Cardiomegaly/genetics, Humans, Serine/metabolism, Chromatin Assembly and Disassembly, Histones/metabolism, hypertrophy, phosphorylated histone 3 serine 28, cardiomyocyte, immediate early genes

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