Key result
The cardiac myocyte epigenome is highly dynamic during development and disease, with distinct epigenetic programs regulating atrial versus ventricular myocytes and driving pathological gene expression.
Why the study?
Recent cell sorting and next generation sequencing techniques have emerged to determine cardiac myocyte-specific transcriptional and epigenetic mechanisms during development, physiological growth, and disease.
This review highlights the dynamic four-dimensional nature of the cardiac myocyte epigenome across development, location, and disease states, offering potential new targets for heart disease treatment.
Dynamic myocyte epigenome may reveal therapeutic targets in heart disease; leaves open clinical translation pending targeted trials.
PURPOSE OF REVIEW: Development, physiological growth and the response of the heart to injury are accompanied by changes of the transcriptome and epigenome of cardiac myocytes. Recently, cell sorting and next generation sequencing techniques have been applied to determine cardiac myocyte-specific transcriptional and epigenetic mechanisms. This review provides a comprehensive overview of studies analysing the transcriptome and epigenome of cardiac myocytes in mouse and human hearts during development, physiological growth and disease. RECENT FINDINGS: Adult cardiac myocytes express > 12,600 genes, and their expression levels correlate positively with active histone marks and inversely with gene body DNA methylation. DNA methylation accompanied the perinatal switch in sarcomere or metabolic isoform gene expression in cardiac myocytes, but remained rather stable in heart disease. DNA methylation and histone marks identified > 100,000 cis-regulatory regions in the cardiac myocyte epigenome with a dynamic spectrum of transcription factor binding sites. The ETS-related transcription factor ETV1 was identified as an atrial-specific element involved in the pathogenesis of atrial fibrillation. Thus, dynamic development of the atrial vs. ventricular cardiac myocyte epigenome provides a basis to identify location and time-dependent mechanisms of epigenetic control to shape pathological gene expression during heart disease. Identifying the four dimensions of the cardiac myocyte epigenome, atrial vs. ventricular location, time during development and growth, and disease-specific signals, may ultimately lead to new treatment strategies for heart disease.
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Rommel et al. (2020) conducted a review in Heart disease and cardiac development. The cardiac myocyte epigenome is highly dynamic during development and disease, with distinct epigenetic programs regulating atrial versus ventricular myocytes and driving pathological gene expression.
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