Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element
Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element
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DOI：
10.1042/bj20020851
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发表时间：
2003-02-01
影响因子：
4.1
通讯作者：
Haro, D
中科院分区：
文献类型：
--
作者：
Barrero, MJ;Camarero, N;Haro, D
一些与脂肪酸代谢有关的基因的表达受过氧化物酶体增殖物激活受体(PPAR)的调节。为了更深入地了解肉碱棕榈酰转移酶(CPT)基因表达的调控，我们研究了人CPT 11基因的转录调控。我们在染色质免疫沉淀实验中证明了该基因的5‘-侧翼区域在转录上是活性的，并在体内与PPARpha结合。此外，我们还鉴定了CPT 11基因启动子近端的PPRE，这似乎是一种新的PPRE。该PPRE的序列包含一个半位点，它是一个完美的共识序列(TGACCT)，但没有明显可识别的第二半位点(CAGCAC)；这部分序列只包含一个与共识的匹配，这似乎与PPARpha的结合无关。正如预期的那样，核受体超家族的其他成员也与该元件结合并抑制PPARpha介导的激活，从而表明几种核受体之间的相互作用可能调节脂肪酸进入线粒体，这是线粒体新陈代谢的关键步骤。
The expression of several genes involved in fatty acid metabolism is regulated by peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of carnitine palmitoyltransferase (CPT) gene expression, we examined the transcriptional regulation of the human CPT 11 gene. We show that the 5'-flanking region of this gene is transcriptionally active and binds PPARalpha in vivo in a chromatin immunoprecipitation assay. In addition, we characterized the peroxisome proliferator-responsive element (PPRE) in the proximal promoter of the CPT 11 gene, which appears to be a novel PPRE. The sequence of this PPRE contains one half-site which is a perfect consensus sequence (TGACCT) but no clearly recognizable second half-site (CAGCAC); this part of the sequence contains only one match to the consensus, which seems to be irrelevant for the binding of PPARalpha. As expected, other members of the nuclear receptor superfamily also bind to this element and repress the activation mediated by PPARalpha, thus showing that the interplay between several nuclear receptors may regulate the entry of fatty acids into the mitochondria, a crucial step in their metabolism.