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KMID : 0624620110440020123
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BMB Reports
2011 Volume.44 No. 2 p.123 ~ p.128
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Cloning and characterization of the cardiac-specific Lrrc10 promoter
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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
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Abstract
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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.
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KEYWORD
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Cardiac-specific, Gata4, Lrrc10, Mef2c, Promoter
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