Cloning and characterization of the cardiac-specific Lrrc10 promoter

• Published in: BMB reports 2011-02, Vol.44 (2), p.123-128
• Main Authors: Fan, Xiongwei, Yang, Qing, Wang, Youliang, Zhang, Yan, Wang, Jian, Yuan, Jiajia, Li, Yongqing, Wang, Yuequn, Deng, Yun, Yuan, Wuzhou, Mo, Xiaoyang, Wan, Yongqi, Ocorr, Karen, Yang, Xiao, Wu, Xiushan
• Format: Article
• Language: Korean
• Subjects: Cardiac-specific; Gata4; Lrrc10; Mef2c; Promoter
• ISSN: 1976-6696; 1976-670X

Leucine-rich repeat containing protein 10 (LRRC10) is characterized as a cardiac-specific gene, suggesting a role in heart development and disease. A severe cardiac morphogenic defect in zebrafish morphants was recently reported but a contradictory result was found in mice, suggesting a more complicated molecular mechanism exists during mouse embryonic development. To elucidate how LRRC10 is regulated, we analyzed the 5`enhancer region approximately 3 kilo bases (kb) upstream of the Lrrc10 start site using luciferase reporter gene assays. Our characterization of the Lrrc10 promoter indicates it possesses complicated cis-and trans-acting elements. We show that GATA4 and MEF2C could both increase transcriptional activity of Lrrc10 promoter individually but that they do not act synergistically, suggesting that there exists a more complex regulation pattern. Surprisingly, knockout of Gata4 and Mef2c binding sites in the 5`enhancer region (-2,894/-2,889) didn`t change the transcriptional activity of the Lrrc10 promoter and the likely GATA4 binding site identified was located in a region only 100 base pair (bp) upstream of the promoter. Our data provides insight into the molecular regulation of Lrrc10 expression, which probably also contributes to its tissue-specific expression. [BMB reports 2011; 44(2): 123-128]