The Histone Methyltransferase EZH2 is Downregulated in the Terminal Differentiation of Cardiomyocytes
10.13865/j.cnki.cjbmb.2025.02.1372
- VernacularTitle:组蛋白甲基化酶EZH2下调参与心肌细胞终末分化
- Author:
Wan-Yi ZHANG
1
;
Wan-Lei ZHANG
;
Yuan-Yuan LIU
;
Ling-Er DING
;
Qi-Kai TANG
;
Zhen-Hang LI
;
Hao-Ying YANG
;
Tao LI
Author Information
1. 湖南师范大学医学技术与转化学院医学免疫学教研室,长沙 410013;模式动物与干细胞生物学湖南重点实验室,长沙 410013
- Publication Type:Journal Article
- Keywords:
enhancer of zeste homolog 2(EZH2);
cardiomyocytes;
terminal differentiation;
cell prolif-eration;
epigenetic modification
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(3):415-425
- CountryChina
- Language:Chinese
-
Abstract:
Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.
