Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 477, Issue -, Pages 1-14Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2018.05.009
Keywords
JMJD3; GSK-J4; beta-MHC; Isoproterenol; Cardiac hypertrophy
Categories
Funding
- National Natural Science Foundation of China [81473205, 81673433]
- National Engineering and Technology Research Center for New drug Drugaability Evaluation (Seed Program of Guangdong Province)
- Major Project of Guangdong Provincial Department of Science and Technology [2015B020232009, 2014B020210003, 2013B090700010]
- Major Project of Platform Construction Education Department of Guangdong Province [2014GKPT002]
- Guangzhou Science and Technology Program Project [201604020121]
- 111 Project of China [B16047]
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Jumonji domain-containing protein D3 (JMJD3), a histone 3 lysine 27 (H3K27) demethylase, has been extensively studied for their participation in development, cellular physiology and a variety of diseases. However, its potential roles in cardiovascular system remain unknown. In this study, we found that JMJD3 played a pivotal role in the process of cardiac hypertrophy. JMJD3 expression was elevated by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of wild-type JMJD3, but not the demethylase-defective mutant, promoted cardiomyocyte hypertrophy, as implied by increased cardiomyocyte surface area and the expression of hypertrophy marker genes. In contrary, JMJD3 silencing or its inhibitor GSK-J4 suppressed ISO-induced cardiac hypertrophy. Mechanistically, JMJD3 was recruited to demethylate H3K27me3 at the promoter of beta-MHC to promote its expression and cardiac hypertrophy. Thus, our results reveal that JMJD3 may be a key epigenetic regulator of beta-MHC expression in cardiomyocytes and a potential therapeutic target for cardiac hypertrophy.
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