{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:39Z","timestamp":1787027799453,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BBS\/E\/B\/000C0400-4"],"award-info":[{"award-number":["BBS\/E\/B\/000C0400-4"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/07\/040\/2289"],"award-info":[{"award-number":["PG\/07\/040\/2289"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Research Foundation - Flanders","doi-asserted-by":"publisher","award":["90663"],"award-info":[{"award-number":["90663"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Research Foundation - Flanders","doi-asserted-by":"publisher","award":["1524317N"],"award-info":[{"award-number":["1524317N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Research Foundation - Flanders","doi-asserted-by":"publisher","award":["G0C6419N"],"award-info":[{"award-number":["G0C6419N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Heart failure is a leading cause of death that develops subsequent to deleterious hypertrophic 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.<\/jats:p>","DOI":"10.3390\/cells11040604","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:19:06Z","timestamp":1644441546000},"page":"604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["MSK-Mediated Phosphorylation of Histone H3 Ser28 Couples MAPK Signalling with Early Gene Induction and Cardiac Hypertrophy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4866-731X","authenticated-orcid":false,"given":"Emma L.","family":"Robinson","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, B-3000 Leuven, Belgium"},{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faye M.","family":"Drawnel","sequence":"additional","affiliation":[{"name":"Epigenetics and Signalling Programmes, Babraham Institute, Cambridge CB22 3AT, UK"},{"name":"Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saher","family":"Mehdi","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline R.","family":"Archer","sequence":"additional","affiliation":[{"name":"Epigenetics and Signalling Programmes, Babraham Institute, Cambridge CB22 3AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1592-6693","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0669-4069","authenticated-orcid":false,"given":"Hanneke","family":"Okkenhaug","sequence":"additional","affiliation":[{"name":"Epigenetics and Signalling Programmes, Babraham Institute, Cambridge CB22 3AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanar","family":"Alkass","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology, Karolinska Institute, SE-17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Magnus","family":"Aronsen","sequence":"additional","affiliation":[{"name":"Institute for Experimental Medical Research, Oslo University Hospital, University of Oslo, 0450 Oslo, Norway"},{"name":"Bj\u00f8rknes College, Oslo University, 0456 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan K.","family":"Nagaraju","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivar","family":"Sjaastad","sequence":"additional","affiliation":[{"name":"Institute for Experimental Medical Research, Oslo University Hospital, University of Oslo, 0450 Oslo, Norway"},{"name":"KG Jebsen Center for Cardiac Research, University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9609-5507","authenticated-orcid":false,"given":"Karin R.","family":"Sipido","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-4107","authenticated-orcid":false,"given":"Olaf","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology, Biomedicum, Karolinska Institutet, SE-17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Simon C.","family":"Arthur","sequence":"additional","affiliation":[{"name":"Division of Immunology and Cell Signalling, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-3523","authenticated-orcid":false,"given":"H. Llewelyn","family":"Roderick","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, B-3000 Leuven, Belgium"},{"name":"KG Jebsen Center for Cardiac Research, University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/eurheartj\/ehz859","article-title":"European Society of Cardiology: Cardiovascular Disease Statistics 2019","volume":"41","author":"Timmis","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.cell.2015.10.035","article-title":"No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice","volume":"163","author":"Alkass","year":"2015","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1476-5381.2012.02195.x","article-title":"The role of the paracrine\/autocrine mediator endothelin-1 in regulation of cardiac contractility and growth","volume":"168","author":"Drawnel","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1161\/CIRCRESAHA.118.311403","article-title":"G-Protein-Coupled Receptors in Heart Disease","volume":"123","author":"Wang","year":"2018","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1161\/CIRCRESAHA.108.188292","article-title":"Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth","volume":"104","author":"Liu","year":"2009","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1152\/physrev.00054.2009","article-title":"Mitogen-activated protein kinase signaling in the heart: Angels versus demons in a heart-breaking tale","volume":"90","author":"Rose","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1093\/emboj\/19.23.6341","article-title":"The MEK1-ERK1\/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice","volume":"19","author":"Bueno","year":"2000","journal-title":"EMBO J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0955-0674(99)80028-3","article-title":"Organization and regulation of mitogen-activated protein kinase signaling pathways","volume":"11","author":"Garrington","year":"1999","journal-title":"Curr. Opin. Cell. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nrm1983","article-title":"Regulation of cardiac hypertrophy by intracellular signalling pathways","volume":"7","author":"Heineke","year":"2006","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1128\/MCB.25.3.865-878.2005","article-title":"Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1\/2 signaling pathways regulate cardiac gene expression and cellular growth","volume":"25","author":"Sanna","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.cellsig.2017.04.010","article-title":"Endothelin-1 promotes hypertrophic remodelling of cardiac myocytes by activating sustained signalling and transcription downstream of endothelin type A receptors","volume":"36","author":"Archer","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13809","DOI":"10.1016\/S0021-9258(18)77420-6","article-title":"Alpha- and beta-adrenergic stimulation induces distinct patterns of immediate early gene expression in neonatal rat myocardial cells. fos\/jun expression is associated with sarcomere assembly; Egr-1 induction is primarily an alpha 1-mediated response","volume":"265","author":"Iwaki","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1073\/pnas.85.2.339","article-title":"Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload","volume":"85","author":"Izumo","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R32","DOI":"10.1186\/gb-2008-9-2-r32","article-title":"Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes","volume":"9","author":"Cullingford","year":"2008","journal-title":"Genome Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/358414a0","article-title":"Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter","volume":"358","author":"Gille","year":"1992","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0955-0674(97)80068-3","article-title":"AP-1 function and regulation","volume":"9","author":"Karin","year":"1997","journal-title":"Curr. Opin. Cell. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1242\/jcs.01589","article-title":"AP-1 subunits: Quarrel and harmony among siblings","volume":"117","author":"Hess","year":"2004","journal-title":"J. Cell. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nrc1209","article-title":"AP-1: A double-edged sword in tumorigenesis","volume":"3","author":"Eferl","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/373257a0","article-title":"Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA","volume":"373","author":"Glover","year":"1995","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/32100","article-title":"Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA","volume":"392","author":"Chen","year":"1998","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.4049\/jimmunol.161.11.6084","article-title":"Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50","volume":"161","author":"Torgerson","year":"1998","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.cardiores.2006.02.032","article-title":"JunD attenuates phenylephrine-mediated cardiomyocyte hypertrophy by negatively regulating AP-1 transcriptional activity","volume":"71","author":"Hilfiker","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1161\/hy0102.100783","article-title":"Dominant negative mutant of c-Jun inhibits cardiomyocyte hypertrophy induced by endothelin 1 and phenylephrine","volume":"39","author":"Omura","year":"2002","journal-title":"Hypertension"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1161\/CIRCULATIONAHA.104.518472","article-title":"Lack of JunD promotes pressure overload-induced apoptosis, hypertrophic growth, and angiogenesis in the heart","volume":"112","author":"Hilfiker","year":"2005","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1101\/gad.327005","article-title":"Distinct functions of junD in cardiac hypertrophy and heart failure","volume":"19","author":"Ricci","year":"2005","journal-title":"Genes Dev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Windak, R., Muller, J., Felley, A., Akhmedov, A., Wagner, E.F., Pedrazzini, T., Sumara, G., and Ricci, R. (2013). The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073294"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1042\/BJ20121371","article-title":"p90 ribosomal S6 kinases play a significant role in early gene regulation in the cardiomyocyte response to G(q)-protein-coupled receptor stimuli, endothelin-1 and alpha(1)-adrenergic receptor agonists","volume":"450","author":"Amirak","year":"2013","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1093\/emboj\/19.14.3714","article-title":"Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation","volume":"19","author":"Clayton","year":"2000","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1242\/jcs.02373","article-title":"MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28 via mitogen- and stress-activated kinase 1\/2","volume":"118","author":"Dyson","year":"2005","journal-title":"J Cell. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1093\/nar\/gkq030","article-title":"Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex","volume":"38","author":"Drobic","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12521","DOI":"10.1074\/jbc.M513333200","article-title":"The kinases MSK1 and MSK2 are required for epidermal growth factor-induced, but not tumor necrosis factor-induced, histone H3 Ser10 phosphorylation","volume":"281","author":"Duncan","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.molcel.2016.09.026","article-title":"Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription","volume":"64","author":"Josefowicz","year":"2016","journal-title":"Mol. Cell."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1093\/emboj\/cdg273","article-title":"MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14","volume":"22","author":"Soloaga","year":"2003","journal-title":"EMBO J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Malakhova, M., Kurinov, I., Liu, K., Zheng, D., D\u2019Angelo, I., Shim, J.H., Steinman, V., Bode, A.M., and Dong, Z. (2009). Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2. PLoS ONE, 4.","DOI":"10.1371\/annotation\/d71909ae-13e2-4fd5-8b17-ca0f13bc38ed"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/BJ20041501","article-title":"MSK1 activity is controlled by multiple phosphorylation sites","volume":"387","author":"McCoy","year":"2005","journal-title":"Biochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4426","DOI":"10.1093\/emboj\/17.15.4426","article-title":"Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2\/p38, and may mediate activation of CREB","volume":"17","author":"Deak","year":"1998","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11010-008-9945-8","article-title":"Differential roles of MAPKs and MSK1 signalling pathways in the regulation of c-Jun during phenylephrine-induced cardiac myocyte hypertrophy","volume":"322","author":"Markou","year":"2009","journal-title":"Mol. Cell. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.yjmcc.2004.08.002","article-title":"Phenylephrine induces activation of CREB in adult rat cardiac myocytes through MSK1 and PKA signaling pathways","volume":"37","author":"Markou","year":"2004","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0014-5793(96)01510-4","article-title":"The protein kinase C inhibitors Ro 318220 and GF 109203X are equally potent inhibitors of MAPKAP kinase-1beta (Rsk-2) and p70 S6 kinase","volume":"402","author":"Alessi","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1042\/bj20011828","article-title":"Phosphorylation and activation of mitogen- and stress-activated protein kinase-1 in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires both extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase","volume":"365","author":"Markou","year":"2002","journal-title":"Biochem. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20110970","article-title":"Characterization of the cellular action of the MSK inhibitor SB-747651A","volume":"441","author":"Naqvi","year":"2012","journal-title":"Biochem. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0014-5793(00)02031-7","article-title":"MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells","volume":"482","author":"Arthur","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1128\/MCB.22.8.2871-2881.2002","article-title":"MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts","volume":"22","author":"Wiggin","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.molcel.2009.02.005","article-title":"Endothelin-1-stimulated InsP3-induced Ca2+ release is a nexus for hypertrophic signaling in cardiac myocytes","volume":"33","author":"Higazi","year":"2009","journal-title":"Mol. Cell."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1083\/jcb.201111095","article-title":"Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy","volume":"199","author":"Drawnel","year":"2012","journal-title":"J. Cell. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1093\/cvr\/cvy088","article-title":"Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons","volume":"114","author":"Dries","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1172\/JCI88353","article-title":"The H3K9 dimethyltransferases EHMT1\/2 protect against pathological cardiac hypertrophy","volume":"127","author":"Thienpont","year":"2017","journal-title":"J. Clin. Invest."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"research0034.1","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1053\/j.seminoncol.2003.08.012","article-title":"CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK)","volume":"30","author":"Allen","year":"2003","journal-title":"Semin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/0006-8993(90)90956-C","article-title":"Effects of endothelin on blood vessels of the brain and choroid plexus","volume":"518","author":"Kadel","year":"1990","journal-title":"Brain Res."},{"key":"ref_52","first-page":"H638","article-title":"Isoproterenol infusion induces alterations in expression of hypertrophy-associated genes in rat heart","volume":"269","author":"Boluyt","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Werhahn, S.M., Kreusser, J.S., Hagenmuller, M., Beckendorf, J., Diemert, N., Hoffmann, S., Schultz, J.H., Backs, J., and Dewenter, M. (2021). Adaptive versus maladaptive cardiac remodelling in response to sustained beta-adrenergic stimulation in a new \u2018ISO on\/off model\u2019. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248933"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"33213","DOI":"10.1074\/jbc.M103973200","article-title":"Ultraviolet B-induced phosphorylation of histone H3 at serine 28 is mediated by MSK1","volume":"276","author":"Zhong","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nature09130","article-title":"Chromatin regulation by Brg1 underlies heart muscle development and disease","volume":"466","author":"Hang","year":"2010","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wang, J.J., Rau, C., Avetisyan, R., Ren, S., Romay, M.C., Stolin, G., Gong, K.W., Wang, Y., and Lusis, A.J. (2016). Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006038"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/0092-8674(91)90385-C","article-title":"Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors","volume":"65","author":"Mahadevan","year":"1991","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1210\/endo.140.5.6699","article-title":"RO 31-8220 activates c-Jun N-terminal kinase and glycogen synthase in rat adipocytes and L6 myotubes. Comparison to actions of insulin","volume":"140","author":"Standaert","year":"1999","journal-title":"Endocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0008-6363(03)00472-3","article-title":"Hypertrophic agonists induce the binding of c-Fos to an AP-1 site in cardiac myocytes: Implications for the expression of GLUT1","volume":"59","author":"Santalucia","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.yjmcc.2014.03.002","article-title":"Targeted deletion of ERK2 in cardiomyocytes attenuates hypertrophic response but provokes pathological stress induced cardiac dysfunction","volume":"72","author":"Ulm","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fphar.2015.00149","article-title":"Extracellular signal-regulated kinases 1\/2 as regulators of cardiac hypertrophy","volume":"6","author":"Mutlak","year":"2015","journal-title":"Front Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1161\/hh2401.100427","article-title":"Increased myocardial Rab GTPase expression: A consequence and cause of cardiomyopathy","volume":"89","author":"Wu","year":"2001","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1161\/CIRCRESAHA.110.231514","article-title":"Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth","volume":"108","author":"Kehat","year":"2011","journal-title":"Circ. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14074","DOI":"10.1073\/pnas.0610906104","article-title":"Genetic inhibition of cardiac ERK1\/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo","volume":"104","author":"Purcell","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.bbrc.2006.03.065","article-title":"JNK1 is required to preserve cardiac function in the early response to pressure overload","volume":"343","author":"Tachibana","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.molcel.2010.08.020","article-title":"Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation","volume":"39","author":"Gehani","year":"2010","journal-title":"Mol. Cell."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.1038\/ncomms6288","article-title":"Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease","volume":"5","author":"Gilsbach","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1016\/j.febslet.2012.06.026","article-title":"H3K27 methylation and H3S28 phosphorylation-dependent transcriptional regulation by INHAT subunit SET\/TAF-Ibeta","volume":"586","author":"Kim","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/path.4489","article-title":"Control of histone H3 phosphorylation by CaMKIIdelta in response to haemodynamic cardiac stress","volume":"235","author":"Awad","year":"2015","journal-title":"J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"22282","DOI":"10.1073\/pnas.1816521116","article-title":"CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation","volume":"116","author":"Saadatmand","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1038\/s41598-018-21372-3","article-title":"Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila","volume":"8","author":"Joos","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7656","DOI":"10.1093\/nar\/gkt500","article-title":"Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy","volume":"41","author":"Awad","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.cellsig.2004.05.001","article-title":"What turns CREB on?","volume":"16","author":"Johannessen","year":"2004","journal-title":"Cell. Signal."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4161\/cc.10.2.14542","article-title":"Double null cells reveal that CBP and p300 are dispensable for p53 targets p21 and Mdm2 but variably required for target genes of other signaling pathways","volume":"10","author":"Kasper","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"H2056","DOI":"10.1152\/ajpheart.00394.2010","article-title":"Cardiac-specific overexpression of dominant-negative CREB leads to increased mortality and mitochondrial dysfunction in female mice","volume":"299","author":"Watson","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41467-021-21188-2","article-title":"Programmable human histone phosphorylation and gene activation using a CRISPR\/Cas9-based chromatin kinase","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/4\/604\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:19Z","timestamp":1760134639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/4\/604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,9]]},"references-count":76,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cells11040604"],"URL":"https:\/\/doi.org\/10.3390\/cells11040604","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,9]]}}}