期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 18, 期 3, 页码 1079-1095出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.65664
关键词
GATA4; Multimerization; Acetylation; Cardiomyocyte; Hypertrophy
资金
- Tokyo Biochemical Research Foundation
- Japan Heart Foundation
- Japan Science and Technology Agency [24890191, 15K09108, 26460071]
- Takeda Science Foundation
- Cardiovascular Research Fund
- Grants-in-Aid for Scientific Research [26460071, 15K09108, 24890191] Funding Source: KAKEN
This study reveals the significance of GATA4 homomultimerization in cardiac hypertrophy, with the acetylation by p300 promoting the multimerization and DNA binding activity of GATA4. Inhibition of GATA4 multimerization suppresses phenylephrine-induced hypertrophic response in cardiomyocytes.
The activation of the GATA-binding factor 4 (GATA4) transcription factor induces cardiac hypertrophy and heart failure. The multimerization of transcription factors often plays an important role in the regulation of transcriptional activity. Here, we report that the GATA4 transcription factor forms a homomultimer and that residues 308-326 of GATA4 are necessary for its multimerization. The acetylation of GATA4 by the transcriptional co-activator p300 induces the multimerization of GATA4 and activates its DNA binding activity. In addition, we found that the suppression of GATA4 multimerization did not reduce its acetylation, but repressed GATA4/p300-induced gene transcription. Furthermore, the inhibition of GATA4 multimerization suppressed phenylephrine (PE)-induced hypertrophic response in cardiomyocytes. This study demonstrates that the multimerization of GATA4 during the p300-induced acetylation of GATA4 activates the transcription of hypertrophic response genes, which leads to cardiomyocyte hypertrophy. Therefore, the inhibition of GATA4 homomultimerization could serve as a potential therapeutic strategy for the development of novel drugs against heart failure.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据