Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy

Papait, Roberto; Serio, Simone; Pagiatakis, Christina; Rusconi, Francesca; Carullo, Pierluigi; Mazzola, Marta; Salvarani, Nicolò; Miragoli, Michele; Condorelli, Gianluigi

doi:10.1161/circulationaha.117.028561

Cited by 87 publications

(69 citation statements)

References 51 publications

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“…As a H3K9me3 demethylase, JMJD2A binds to FHL1 promoter and promotes cardiac hypertrophy . By interacting with PRC2, G9a catalyses the formation of H3K9me3, which inhibits the expression of anti‐cardiac hypertrophy genes mediated by the MEF2C complex . In this study, we found that H3K27me2 and H3K36me2 participate in the pathogenesis of ventricular remodelling which is associated with NSD2.…”

Section: Discussionmentioning

confidence: 58%

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NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2

Zhou

Zhu²,

et al. 2018

J Cellular Molecular Medi

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Histone lysine methylation plays an important role in the regulation of ventricular remodelling. NSD2 is involved in many types of tumours through enhancing H3K36me2 expression. However, the role of NSD2 in the regulation of histone lysine methylation during ventricular remodelling remains unclear. In this study, we established cardiac hypertrophy model in C57BL/6 mice by transverse aortic constriction and found that histone lysine methylation participated in ventricular remodelling regulation via the up‐regulation of H3K27me2 and H3K36me2 expression. In addition, we constructed transgenic C57BL/6 mice with conditional knockout of NSD2 (NSD2−/−) in the myocardium. NSD2−/− C57BL/6 mice had milder ventricular remodelling and significantly improved cardiac function compared with wild‐type mice, and the expression of H3K36me2 but not H3K27me2 was down‐regulated. In conclusion, NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2.

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Section: Discussionmentioning

confidence: 58%

“…HKM plays an important role in the regulation of ventricular remodelling . For example, H3K9me2 and H3K9me3 can inhibit pathological myocardial hypertrophy . NSD2 (The Nuclear SET Domain 2) is one of the major members of the NSD family and is highly expressed in the myocardium.…”

Section: Introductionmentioning

confidence: 99%

NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2

Zhou

Zhu²,

et al. 2018

J Cellular Molecular Medi

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“…This aberrant DNA methylation was associated with decreased mRNA expression of these two transcription factors, suggesting that DNA methylation plays a key role in transcriptional regulation and pathophysiology of TOF. Similarly, the histone methyltransferase G9a is well‐known to regulate the expression of MEF2C , a transcription factor associated with outflow tract anomalies . While we are learning the importance of transcription factors in the development of CHD, it will be vital to understand the epigenetic regulation of transcription factors.…”

Section: Impact Of Epigenetics In Congenital and Acquired Pediatric Hmentioning

confidence: 99%

“…Similarly, the histone methyltransferase G9a is well-known to regulate the expression of MEF2C, a transcription factor associated with outflow tract anomalies. [23][24][25] While we are learning the importance of transcription factors in the development of CHD, it will be vital to understand the epigenetic regulation of transcription factors.…”

Section: M P a Ct Of E P I Gen E Ti Cs I N Con Ge N It Al A N D Amentioning

confidence: 99%

Epigenetics for the pediatric cardiologist

Spearman

2017

Congenital Heart Disease

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A genetic basis of congenital heart disease (CHD) has been known for decades. In addition to the sequence of the genome, the contribution of epigenetics to pediatric cardiology is increasingly recognized. Multiple epigenetic mechanisms, including DNA methylation, histone modification, and RNA-based regulation, are known mediators of cardiovascular disease, including both development and progression of CHD and its sequelae. Basic understanding of the concepts of epigenetics will be essential to all pediatric cardiologists in order to understand mechanisms of pathophysiology, pharmacotherapeutic concepts, and to understand the role of epigenetics in precision medicine.

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“…While heart failure is accompanied by two pathological processes, cardiac hypertrophy and cardiac fibrosis, the underlying source results from alterations of gene expression. Cardiac hypertrophy is accompanied by an increase of expression of fetal cardiac genes (e.g., Nppa, Nppb, Myh7 and Skeletal Alpha-Actin) and repression of adult genes (e.g., Myh6), while cardiac fibrosis is a result of an increase of expression of genes encoding proteins of the extracellular matrix (e.g., collagens), processes for which the specific underlying mechanisms still remain unknown [5].…”

Section: Introductionmentioning

confidence: 99%

Epigenetics of aging and disease: a brief overview

et al. 2019

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Aging is an important risk factor for several human diseases such as cancer, cardiovascular disease and neurodegenerative disorders, resulting from a combination of genetic and environmental factors (e.g., diet, smoking, obesity and stress), which, at molecular level, cause changes in gene expression underlying the decline of physiological function. Epigenetics, which include mechanisms regulating gene expression independently of changes to DNA sequence, regulate gene expression by modulating the structure of chromatin or by regulating the binding of transcriptional machinery to DNA. Several studies showed that an impairment of epigenetic mechanisms promotes alteration of gene expression underlying several aging-related diseases. Alteration of these mechanisms is also linked with changes of gene expression that occurs during aging processes of different tissues. In this review, we will outline the potential role of epigenetics in the onset of two age-related pathologies, cancer and cardiovascular diseases.

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Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy

Abstract: Taken together, our findings demonstrate that G9a orchestrates critical epigenetic changes in cardiomyocytes in physiological and pathological conditions, thereby providing novel therapeutic avenues for cardiac pathologies associated with dysregulation of these mechanisms.

Cited by 87 publications

References 51 publications

NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2

NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2

Epigenetics for the pediatric cardiologist

Epigenetics of aging and disease: a brief overview

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