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NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation
Li, Wei ; Zheng, Nai-Zhong ; Yuan, Qi ; Xu, Ke ; Yang, Fan ; Gu, Lei ; Zheng, Gu-Yan ; Luo, Guo-Jie ; Fan, Chun ; Ji, Guang-Ju ; Zhang, Bo ; Cao, Huiqing ; Tian, Xiao-Li
刊名JOURNAL OF MOLECULAR MEDICINE-JMM
2016
关键词L-type calcium channel NFAT5 Cardiac development Comparative genomic Transcriptional factor CA2+ CHANNEL CALCIUM-CHANNELS GENE-EXPRESSION VENTRICULAR MYOCYTES COMPARATIVE GENOMICS MOUSE HEART MICE CARDIOMYOCYTES IDENTIFICATION MUSCLE
DOI10.1007/s00109-016-1444-x
英文摘要Entry of calcium into cardiomyocyte via L-type calcium channel (LTCC) is fundamental to cardiac contraction. CACNA1C, a type of LTCC and a hallmark of a matured ventricular myocyte, is developmentally regulated. Here, we identified 138 potential transcription factors by a comparative genomic study on 5-kb promoter regions of CACNA1C gene across eight vertebrate species, and showed that six factors were developmentally regulated with the expression of Cacna1c in mouse P19cl6 in vitro cardiomyocyte differentiation model. We further demonstrated that the nuclear factor of activated T cells 5 (Nfat5) bound to a consensus sequence TGGAAGCGTTC and activated the transcription of Cacna1c. The siRNA-mediated knockdown of Nfat5 suppressed the expression of Cacna1c and decreased L-type calcium current in mouse neonatal cardiomyocytes. Furthermore, morpholino-mediated knockdown of nfat5 in zebrafish prohibited the expression of cacna1c and resulted in a non-contractile ventricle, while over-expression of either cacna1c or nfat5 rescued this impaired phenotype. Thus, NFAT5-mediated expression of CACNA1C is evolutionarily conserved and critical for cardiac electrophysiological development and maturation of cardiomyocyte.; National Basic Research Program of the Chinese Ministry of Science and Technology (973 grant) [2013CB530700, 2007CB512103, 2012CB945101]; SCI(E); PubMed; ARTICLE; caohuiqing@pku.edu.cn; tianxiaoli@pku.edu.cn; 9; 993-1002; 94
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/448028]  
专题生命科学学院
信息科学技术学院
推荐引用方式
GB/T 7714
Li, Wei,Zheng, Nai-Zhong,Yuan, Qi,et al. NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2016.
APA Li, Wei.,Zheng, Nai-Zhong.,Yuan, Qi.,Xu, Ke.,Yang, Fan.,...&Tian, Xiao-Li.(2016).NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation.JOURNAL OF MOLECULAR MEDICINE-JMM.
MLA Li, Wei,et al."NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation".JOURNAL OF MOLECULAR MEDICINE-JMM (2016).
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