Cloning of the human cholesteryl ester hydrolase promoter: Identification of functional peroxisomal proliferator-activated receptor responsive elements
Cloning of the human cholesteryl ester hydrolase promoter: Identification of functional peroxisomal proliferator-activated receptor responsive elements
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DOI：
10.1006/bbrc.2001.5078
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发表时间：
2001-06-22
影响因子：
3.1
通讯作者：
Natarajan, R
中科院分区：
文献类型：
--
作者：
Ghosh, S;Natarajan, R
胆固醇酯水解酶（CEH）负责水解巨噬细胞泡沫细胞中储存的胆固醇酯，并释放游离胆固醇用于高密度脂蛋白介导的外排。用人巨噬细胞CEH特异性引物对人基因组文库进行基于PCR的筛选，扩增并克隆了1.7 kb启动子序列。序列分析显示缺乏共识TATA盒，但存在富含GC的近端序列、CAAT盒和转录因子Spl的几个结合位点。在-176、-779和-1.316位鉴定了过氧化物酶体增殖物激活受体（PPRE）的三个假定反应元件。在PPARalpha-或PPARgamma-特异性配体存在下观察到启动子活性的下调，并且在PPRE中在-176处引入4点横向突变完全消除了PPARalpha-或PPARgamma-特异性配体对启动子活性的影响。与参与巨噬细胞胆固醇稳态的其他基因类似，人CEH也可能受PPAR调节。(C)北京：科学出版社.
Cholesteryl ester hydrolase (CEH) is responsible for hydrolysis of stored cholesterol esters in macrophage foam cells and release of free cholesterol for high-density lipoprotein-mediated efflux. PCR-based screening of human genomic libraries with human macrophage CEH specific primers resulted in amplification and cloning of 1.7 kb promoter sequence. Analysis of the sequence revealed a lack of consensus TATA-box but presence of a GC-rich proximal sequence, a CAAT box and several binding sites for the transcription factor Spl. Three putative response elements for peroxisome proliferator-activated receptor (PPRE) were identified at position -176, -779, and -1.316. Downregulation of promoter activity was observed in the presence of either PPAR alpha- or PPAR gamma -specific ligands and introduction of a 4-point transverse mutation in the PPRE at -176 completely abolished the effect of PPAR ligands on the promoter activity. Analogous to other genes involved in macrophage cholesterol homeostasis, human CEH may also be regulated by PPAR. (C) 2001 Academic Press.