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学科主题基础医学
GATA4 regulates ANF expression synergistically with Sp1 in a cardiac hypertrophy model
Hu, Xiaoqing1; Li, Tao2; Zhang, Chenguang1; Liu, Yinan1; Xu, Ming3,4; Wang, Weiping1,4; Jia, Zhuqing1,4; Ma, Kangtao1,4; Zhang, Youyi3,4; Zhou, Chunyan1,4
关键词GATA4 Sp1 Sp3 ANF expression cardiac hypertrophy transcription
刊名JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
2011-09-01
DOI10.1111/j.1582-4934.2010.01182.x
15期:9页:1865-1877
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]Cell Biology ; Research & Experimental Medicine
关键词[WOS]TRANSCRIPTION FACTOR GATA-4 ; ACTIVATED PROTEIN-KINASES ; SERUM RESPONSE FACTOR ; HEART TUBE FORMATION ; GENE-EXPRESSION ; VENTRAL MORPHOGENESIS ; SIGNALING PATHWAY ; SP-FAMILY ; CARDIOMYOCYTES ; PHOSPHORYLATION
英文摘要

Cardiac hypertrophy in response to multiple stimuli has important physiological and pathological significances. GATA4 serves as a nuclear integrator of several signalling pathways during cardiac hypertrophy. Sp1 and Sp3 are also reported to be involved in this process. However, the mechanism by which GATA4 acts as a mediator, integrating these ubiquitously expressed transcriptional factors, is poorly understood. We found that the expression of GATA4 and Sp1 was up-regulated in the myocardium of a pressure overload hypertrophy rat model, as well in phenylephrine-induced (PE-induced) hypertrophic growth of neonatal cardiomyocytes. GST pull-down assays demonstrated that GATA4 could interact with Sp1 in vitro. Therefore, we proposed that GATA4 cooperates with Sp1 in regulating ANF expression, as its reactivation is closely linked with hypertrophy. Further studies demonstrated that GATA4 could activate the ANF promoter synergistically with Sp1 through direct interaction. In contrast, Sp3 exhibited antagonistic function, and overexpression of Sp3 repressed the transcriptional synergy between Sp1 and GATA4. We also found that Sp1 alone could activate the ANF promoter in cardiomyocytes, whereas Sp3 exerted negative effects on ANF expression. Bioinformatics analysis revealed novel Sp-binding sites on the ANF promoter. The recruitment of GATA4 and Sp1 on the ANF promoter was enhanced during phenylephrine-mediated hypertrophy, whereas the recruitment of Sp3 was reduced. The phosphorylation of GATA4 by ERK1/2 kinase could enhance the affinity between GATA4 and Sp1. Thus, our findings revealed the critical interaction of GATA4 and Sp1 in modulating ANF expression, indicating their involvement in cardiac hypertrophy.

语种英语
WOS记录号WOS:000294597400007
项目编号30871253 ; 90919022 ; B07001
资助机构National Natural Sciences Foundation of China ; 111 Project of China
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60035
专题北京大学基础医学院
作者单位1.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
2.Zhejiang Normal Univ, Dept Biol, Coll Chem & Life Sci, Jinhua, Zhejiang, Peoples R China
3.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100191, Peoples R China
4.Peking Univ, Minist Educ China, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
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GB/T 7714
Hu, Xiaoqing,Li, Tao,Zhang, Chenguang,et al. GATA4 regulates ANF expression synergistically with Sp1 in a cardiac hypertrophy model[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2011,15(9):1865-1877.
APA Hu, Xiaoqing.,Li, Tao.,Zhang, Chenguang.,Liu, Yinan.,Xu, Ming.,...&Zhou, Chunyan.(2011).GATA4 regulates ANF expression synergistically with Sp1 in a cardiac hypertrophy model.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,15(9),1865-1877.
MLA Hu, Xiaoqing,et al."GATA4 regulates ANF expression synergistically with Sp1 in a cardiac hypertrophy model".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 15.9(2011):1865-1877.
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