title: Cloning and characterization of the cardiac-specific Lrrc10 promoter.
abstract: 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.
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Fan
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Youliang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yuan
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Li
authors.forename: Yuequn
authors.initials: Y
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Deng
authors.forename: Wuzhou
authors.initials: W
authors.lastname: Yuan
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Mo
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Wan
authors.forename: Karen
authors.initials: K
authors.lastname: Ocorr
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Xiushan
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D064326:MEF2 Transcription Factors; D051379:Mice; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; C482740:heart-restricted leucine-rich repeat protein, mouse