Cloning and characterization of the cardiac-specific Lrrc10 promoter
2011; Korean Society for Biochemistry and Molecular Biology; Volume: 44; Issue: 2 Linguagem: Inglês
10.5483/bmbrep.2011.44.2.123
ISSN1976-670X
AutoresXiongwei Fan, Qing Yang, Youliang Wang, Yan Zhang, Jian Wang, Jiajia Yuan, Yongqing Li, Yuequn Wang, Yun Deng, Wuzhou Yuan, Xiaoyang Mo, Yongqi Wan, Karen Ocorr, Xiao Yang, Xiushan Wu,
Tópico(s)Pluripotent Stem Cells Research
ResumoLeucine-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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