Functional interaction between peroxisome proliferator-activated receptors-α and Mef-2C on human carnitine palmitoyltransferase 1β (CPT1β) gene activation
Functional interaction between peroxisome proliferator-activated receptors-α and Mef-2C on human carnitine palmitoyltransferase 1β (CPT1β) gene activation
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DOI：
10.1093/nar/gkh806
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Haro, D
中科院分区：
文献类型：
--
作者：
Baldán, A;Relat, J;Haro, D
肌肉型肉毒碱棕榈酰转移酶1（CPT 1 β）被认为是控制脂肪酸线粒体β-氧化的基因。一个功能性过氧化物酶体增殖物激活受体（PPAR）反应元件（PPRE）和一个myocite特异性（MEF 2）的网站，结合MEF 2A和MEF 2C在该基因的启动子已被确定。我们研究了PPRE和MEF 2结合位点的作用以及PPARalpha和MEF 2C调节CPT 1 β基因启动子之间的潜在相互作用。突变分析表明，MEF 2位点在C2 C12细胞中通过PPAR激活CPT 1 β启动子中起作用。含有PPRE和MEF 2C位点的报告构建体通过在非肌肉细胞中共表达PPAR、类维生素A X受体（RXR）和MEF 2C而协同激活。此外，蛋白结合试验表明，MEF 2C和PPAR特异性结合在体外。同样，对于MEF 2C和PPARalpha-RXR α协同激活CPT 1 β基因启动子，其结合位点的精确排列是必不可少的。
Muscle-type carnitine palmitoyltransferase 1 (CPT1beta) is considered to be the gene that controls fatty acid mitochondrial beta-oxidation. A functional peroxisome proliferator-activated receptor (PPAR) responsive element (PPRE) and a myocite-specific (MEF2) site that binds MEF2A and MEF2C in the promoter of this gene had been previously identified. We investigated the roles of the PPRE and the MEF2 binding sites and the potential interaction between PPARalpha and MEF2C regulating the CPT1beta gene promoter. Mutation analysis indicated that the MEF2 site contributed to the activation of the CPT1beta promoter by PPAR in C2C12 cells. The reporter construct containing the PPRE and the MEF2C site was synergistically activated by co-expression of PPAR, retinoid X receptor (RXR) and MEF2C in non-muscle cells. Moreover, protein-binding assays demonstrated that MEF2C and PPAR specifically bound to one another in vitro. Also for the synergistic activation of the CPT1beta gene promoter by MEF2C and PPARalpha-RXRalpha, a precise arrangement of its binding sites was essential.