Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy
Authors: Gillian H Little
Yan Bai
Woojin An
Larry Kedes
Muhammad Kunhi
Donald Bers
Coralie Poizat
Salma Awad
Journal: Nucleic Acids Research (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CaMKII; cardiac hypertrophy; chromatin; histone H3 phosphorylation; gene activity
Affiliations: Cardiovascular Research Program, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Kingdom of Saudi Arabia, Institute for Genetic Medicine, University of Southern California 2250 Alcazar Street, Los Angeles, CA 90033, USA, Department of Biochemistry and Molecular Biology, University of Southern California 2250 Alcazar Street, Los Angeles, CA 90089, USA, Department of Pharmacology, University of California at Davis, Davis, CA 95616, USA and Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA.

Abstract:  Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity in the nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates cardiac transcription by directly binding to chromatin and regulating the phosphorylation of histone H3 at serine-10. These specific activities are demonstrated both in vitro and in primary neonatal rat cardiomyocytes. Activation of CaMKII signaling by hypertrophic agonists increases H3 phosphorylation in primary cardiac cells and is accompanied by concomitant cellular hypertrophy. Conversely, specific silencing of nuclear CaMKII using RNA interference reduces both H3 phosphorylation and cellular hypertrophy. The hyper-phosphorylation of H3 associated with increased chromatin binding of CaMKII occurs at specific gene loci reactivated during cardiac hypertrophy. Importantly, H3 Ser-10 phosphorylation and CaMKII recruitment are associated with increased chromatin accessibility and are required for chromatin-mediated transcription of the Mef2 transcription factor. Unlike phosphorylation of H3 by other kinases, which regulates cellular proliferation and immediate early gene activation, CaMKII-mediated signaling to H3 is associated with hypertrophic growth. These observations reveal a previously unrecognized function of CaMKII as a kinase signaling to histone H3 and remodeling chromatin. They suggest a new epigenetic mechanism controlling cardiac hypertrophy. 

Retracted: No

PubPeer comments:
 image duplication ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 I agree with the above concern. In addition, in Figure 7, it appears some of the assays have been used to represent multiple conditions. *** ![file] , 
 Expression of Concern on u2018Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophyu2019 https: academic.oup.com nar advance-article doi 10.1093 nar gkac721 6671108 The Editors were alerted in 2022 about potential issues with Figures 4B, 7C, and 7D. While the Editors work with the authors and institution where the research was conducted to retrieve the original data, we advise readers to examine the details of this study with particular care. Julian E. Sale, Barry L. Stoddard Senior Executive Editors ,