Related Experiment Video
Updated: Feb 25, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy
Roberto Papait1, Simone Serio2, Christina Pagiatakis2
1From Department of Cardiovascular Medicine, Humanitas Research Hospital, Rozzano, Milan, Italy (R.P., S.S., C.P., F.R., P.C., N.S., M. Miragoli, G.C.); Genetic and Biomedical Research Institute, National Research Council of Italy, Rozzano, Milan, Italy (R.P., F.R., P.C., N.S., G.C.); Humanitas University, Rozzano, Milan, Italy (M. Mazzola, G.C.); School of Medicine, University of Verona, Italy (M. Mazzola); and Department of Medicine and Surgery, University of Parma, Italy (M. Miragoli). roberto.papait@humanitasresearch.it gianluigi.condorelli@hunimed.eu.
Background:
Correct gene expression programming of the cardiomyocyte underlies the normal functioning of the heart. Alterations to this can lead to the loss of cardiac homeostasis, triggering heart dysfunction. Although the role of some histone methyltransferases in establishing the transcriptional program of postnatal cardiomyocytes during heart development has been shown, the function of this class of epigenetic enzymes is largely unexplored in the adult heart. In this study, we investigated the role of G9a/Ehmt2, a histone methyltransferase that defines a repressive epigenetic signature, in defining the transcriptional program for cardiomyocyte homeostasis and cardiac hypertrophy.
Methods:
We investigated the function of G9a in normal and stressed cardiomyocytes with the use of a conditional, cardiac-specific G9a knockout mouse, a specific G9a inhibitor, and high-throughput approaches for the study of the epigenome (chromatin immunoprecipitation sequencing) and transcriptome (RNA sequencing); traditional methods were used to assess cardiac function and cardiovascular disease.
Results:
We found that G9a is required for cardiomyocyte homeostasis in the adult heart by mediating the repression of key genes regulating cardiomyocyte function via dimethylation of H3 lysine 9 and interaction with enhancer of zeste homolog 2, the catalytic subunit of polycomb repressive complex 2, and MEF2C-dependent gene expression by forming a complex with this transcription factor. The G9a-MEF2C complex was found to be required also for the maintenance of heterochromatin needed for the silencing of developmental genes in the adult heart. Moreover, G9a promoted cardiac hypertrophy by repressing antihypertrophic genes.
Conclusions:
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.
More Related Videos
10:05Improved Generation of Induced Cardiomyocytes Using a Polycistronic Construct Expressing Optimal Ratio of Gata4, Mef2c and Tbx5
Published on: November 13, 2015
09:29Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
Related Concept Videos
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:30General Transcription Factors
02:32Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
01:13Structure of Cardiac Muscles
Compared to skeletal muscles, cardiac muscle cells are small and mostly have a single nucleus. Additionally, they are usually...
02:23Master Transcription Regulators
01:32Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...