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Histone H4R3 symmetric di-methylation by Prmt5 protects against cardiac hypertrophy via regulation of Filip1L/β-catenin.
- Source :
-
Pharmacological research [Pharmacol Res] 2020 Nov; Vol. 161, pp. 105104. Date of Electronic Publication: 2020 Jul 31. - Publication Year :
- 2020
-
Abstract
- Background and Purpose: Although histone lysine methylation has been extensively studied for their participation in pathological cardiac hypertrophy, the potential regulatory role of histone arginine methylation remains to be elucidated. The present study focused on H4R3 symmetric di-methylation (H4R3me2s) induced by protein arginine methyltransferase 5 (Prmt5), and explored its epigenetic regulation and underlying mechanisms in cardiomyocyte hypertrophy.<br />Methods and Results: 1. The expressions of Prmt5 and H4R3me2s were suppressed in cardiac hypertrophy models in vivo and in vitro; 2. Prmt5 silencing or its inhibitor EPZ, or knockdown of cooperator of Prmt5 (Copr5) to disrupt H4R3me2s, facilitated cardiomyocyte hypertrophy, whereas overexpression of wild type Prmt5 rather than the inactive mutant protected cardiomyocytes against hypertrophy; 3. ChIP-sequence analysis identified Filip1L as a target gene of Prmt5-induced H4R3me2s; 4. Knockdown or inhibition of Prmt5 impaired Filip1L transcription and subsequently prevented β-catenin degradation, thus augmenting cardiomyocyte hypertrophy.<br />Conclusions: The present study reveals that Prmt5-induced H4R3me2s ameliorates cardiomyocyte hypertrophy by transcriptional upregulation of Filip1L and subsequent enhancement of β-catenin degradation. Deficiency of Prmt5 and the resulting suppression of H4R3me2s might facilitate the development of pathological cardiac hypertrophy. Prmt5 might serve as a key epigenetic regulator in pathological cardiac hypertrophy.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Arginine
Cells, Cultured
Disease Models, Animal
Epigenesis, Genetic
Hypertrophy, Left Ventricular genetics
Hypertrophy, Left Ventricular pathology
Hypertrophy, Left Ventricular physiopathology
Male
Methylation
Mice, Inbred C57BL
Myocytes, Cardiac pathology
Protein-Arginine N-Methyltransferases genetics
Rats, Sprague-Dawley
Signal Transduction
Histones metabolism
Hypertrophy, Left Ventricular enzymology
Myocytes, Cardiac enzymology
Protein-Arginine N-Methyltransferases metabolism
Ventricular Function, Left
Ventricular Remodeling
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1186
- Volume :
- 161
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 32739429
- Full Text :
- https://doi.org/10.1016/j.phrs.2020.105104