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首页> 外文期刊>BMC Molecular Biology >Cooperation between MEF2 and PPAR gamma in human intestinal ,beta,beta-carotene 15,15'-monooxygenase gene expression
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Cooperation between MEF2 and PPAR gamma in human intestinal ,beta,beta-carotene 15,15'-monooxygenase gene expression

机译：MEF2与PPARγ在人肠道，β，β-胡萝卜素15,15'-单加氧酶基因表达中的合作

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Background: Vitamin A and its derivatives,the retinoids,are essential for normal embryonic development and maintenance of cell differentiation.beta,beta -carotene 15,15'-monooxygenase 1 (BCMO1) catalyzes the central cleavage of beta-carotene to all-trans retinal and is the key enzyme in the intestinal metabolism of carotenes to vitamin A.However,human and various rodent species show markedly different efficiencies in intestinal BCMO1-mediated carotene to retinoid conversion.The aim of this study is to identify potentially human-specific regulatory control mechanisms of BCMO1 gene expression.Results: We identified and functionally characterized the human BCMO1 promoter sequence and determined the transcriptional regulation of the BCMO1 gene in a BCMO1 expressing human intestinal cell line,TC-7.Several functional transcription factor-binding sites were identified in the human promoter that are absent in the mouse BCMO1 promoter.We demonstrate that the proximal promoter sequence,nt -190 to +35,confers basal transcriptional activity of the human BCMO1 gene.Site-directed mutagenesis of the myocyte enhancer factor 2 (MEF2) and peroxisome proliferator-activated receptor (PPAR) binding elements resulted in decreased basal promoter activity.Mutation of both promoter elements abrogated the expression of intestinal cell BCMO1.Electrophoretic mobility shift and supershift assays and transcription factor co-expression in TC-7 cells showed MEF2C and PPAR gamma bind to their respective DNA elements and synergistically transactivate BCMO1 expression.Conclusions: We demonstrate that human intestinal cell BCMO1 expression is dependent on the functional cooperation between PPAR and MEF2 isoforms.The findings suggest that the interaction between MEF2 and PPAR factors may provide a molecular basis for interspecies differences in the transcriptional regulation of the BCMO1 gene.
机译：背景：维生素A及其衍生物类维生素A是正常胚胎发育和维持细胞分化所必需的。β，β-胡萝卜素15,15'-单加氧酶1（BCMO1）催化β-胡萝卜素向全反式的中心裂解。视网膜是胡萝卜素转化为维生素A的肠道代谢中的关键酶。然而，人类和各种啮齿动物物种在肠道BCMO1介导的胡萝卜素向类维生素A转化方面显示出明显不同的效率。结果：我们鉴定了人BCMO1启动子序列并对其进行了功能表征，并确定了表达BCMO1的人肠道细胞系TC-7中BCMO1基因的转录调控，并鉴定了几个功能性转录因子结合位点。在小鼠BCMO1启动子中不存在的人类启动子中。我们证明了近端启动子序列nt -190 t +35，赋予人BCMO1基因基础转录活性。肌细胞增强子因子2（MEF2）和过氧化物酶体增殖物激活受体（PPAR）结合元件的位点诱变导致基础启动子活性降低。 TC-7细胞的电泳迁移率迁移和超迁移测定以及转录因子共表达表明，MEF2C和PPARγ与其各自的DNA元件结合，并协同反式激活BCMO1表达。结论：我们证明了人类肠道细胞BCMO1的表达取决于PPAR和MEF2亚型之间的功能合作。研究结果表明，MEF2和PPAR因子之间的相互作用可能为BCMO1基因转录调控中的种间差异提供分子基础。

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