@article{c6e35814daf843cc97fe3ec20f2d2730,
title = "MSK-Mediated Phosphorylation of Histone H3 Ser28 Couples MAPK Signalling with Early Gene Induction and Cardiac Hypertrophy",
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.",
keywords = "Cardiomyocyte, Hypertrophy, Immediate early genes, MSK, Phosphorylated histone 3 serine 28",
author = "Robinson, {Emma L.} and Drawnel, {Faye M.} and Saher Mehdi and Archer, {Caroline R.} and Wei Liu and Hanneke Okkenhaug and Kanar Alkass and Aronsen, {Jan Magnus} and Nagaraju, {Chandan K.} and Ivar Sjaastad and Sipido, {Karin R.} and Olaf Bergmann and Arthur, {J. Simon C.} and Xin Wang and Roderick, {H. Llewelyn}",
note = "Funding Information: This work was supported by an Odysseus Award and project grants from the Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek; FWO, 90663 and G0C6419N), the Babraham Institute, the Biotechnology and Biological Sciences Research Council (BBSRC, BBS/E/B/0000C116, BBS/E/B/000C0402) and The Royal Society (University Research Fellowship to H.L.R., UF041311). F.M.D. and C.R.A. were supported by studentships from the BBSRC (BBS/E/B/0000L715 and BBS/E/B/0000L726, respectively). E.L.R. was funded through a Wellcome Trust PhD fellowship (Cardiovascular & Disease), an international scholarship from the KU Leuven Faculty of Medicine and an American Heart Association Postdoctoral fellowship (829504). SM received a research grant from the FWO (1524317N). O.B. was supported by the Center for Regenera-tive Therapies Dresden, the Karolinska Institutet, the Swedish Research Council, the Ragnar S?derberg Foundation, the ?ke Wiberg Foundation, and the LeDucq foundation. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
month = feb,
day = "9",
doi = "10.3390/cells11040604",
language = "English",
volume = "11",
pages = "1--27",
journal = "Cells",
issn = "2073-4409",
publisher = "MDPI",
number = "4",
}