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  • Review Article
  • Published:

Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure

Nature Reviews Cardiology volume 12, pages 488–497 (2015)Cite this article

Subjects

Key Points

  • The myocardium adapts to continued stress—either physiological or pathological—by modulating gene expression in its constituent cells

  • Methylation of cytosine and post-translational chemical alteration of histones—known as epigenetic modification—render regulatory elements of genes more or less permissive to interaction with the transcriptional machinery

  • These alterations create an epigenetic landscape, or 'epigenome', that is probably specific to a particular physiological or pathological state

  • A plethora of noncoding RNAs, such as microRNAs and long noncoding RNAs, is centrally involved in the regulation of probably all biological processes, including gene expression

  • Epigenetic modifications and noncoding RNAs form an integrated and highly complex regulatory network to control gene expression; heart failure is associated with disruption of this network

  • The reversibility of epigenetic modifications and the relative ease with which noncoding RNAs can be manipulated augur well for the development of much-needed novel pharmaceuticals for treatment of heart failure

Abstract

The regulatory networks governing gene expression in cardiomyocytes are under intense investigation, not least because dysregulation of the gene programme has a fundamental role in the development of a failing myocardium. Epigenetic modifications and functional non-protein-coding RNAs (ncRNAs) are important contributors to this process. The epigenetic modifications that regulate transcription comprise post-translational changes to histones—the proteins around which DNA is wound—as well as modifications to cytosine residues on DNA. The most studied of the histone changes are acetylation and methylation. Histone acetylation is known to be important in cardiac physiology and pathophysiology, but the roles of other histone modifications and of cytosine methylation are only starting to be investigated. Understanding of the role of microRNAs has also seen major advancements, but the function of long ncRNAs is less well defined. Moreover, the connection between ncRNAs and epigenetic modifications is poorly understood in the heart. In this Review, we summarize new insights into how these two layers of gene-expression regulation might be involved in the pathogenesis of cardiac hypertrophy and failure, and how we are only beginning to appreciate the complexity of the interactive network of which they are part.

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Figure 1: DNA and chromatin modifications in gene-expression regulation.
Figure 2: miRNA biogenesis and function.
Figure 3: Mechanisms of action of lncRNAs.

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Acknowledgements

G.C. is funded by grants from the European Research Council ('Advanced' grant CARDIOEPIGEN n.294609), and the Italian Ministry of Education, University and Research (MIUR) (n.2010RNXM9C). G.C. is also affiliated with the Institute of Genetic and Biomedical Research (IGBR), National Research Council of Italy, and the Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

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  1. Humanitas Clinical and Research Hospital, University of Milan, Via Manzoni 56, Milan, 20089, Rozzano, Italy

    Carolina M. Greco & Gianluigi Condorelli

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C.M.G. researched data for the article. Both authors discussed the content of the article, wrote the manuscript, and reviewed/edited it before submission.

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Correspondence to Gianluigi Condorelli.

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The authors declare no competing financial interests.

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Greco, C., Condorelli, G. Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure. Nat Rev Cardiol 12, 488–497 (2015). https://doi.org/10.1038/nrcardio.2015.71

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