Identification of peroxisome-proliferator responsive element in the mouse HSL gene
Identification of peroxisome-proliferator responsive element in the mouse HSL gene
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DOI：
10.1016/j.bbrc.2006.11.054
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发表时间：
2007-01-12
影响因子：
3.1
通讯作者：
Horino, Yoko
中科院分区：
文献类型：
--
作者：
Yajima, Hiroaki;Kobayashi, Yumie;Horino, Yoko
激素敏感脂肪酶(HSL)催化脂肪组织中脂肪分解的限速步骤。一些研究表明，蛋白质磷酸化调节HSL的酶活性。另一方面，HSL基因转录调控的确切机制仍有待阐明。在这里，我们利用5‘-侧翼区的序列缺失和点突变，在CV-1细胞中通过报告实验鉴定了小鼠HSL启动子中的一个功能性过氧化物体-增殖物反应元件(PPRE)。染色质免疫沉淀(ChIP)分析显示，过氧化物酶体增殖物激活受体(PPAR-γ)和维甲酸X受体(RXRα)均与该区域相互作用。电泳迁移率改变分析也证实了PPARγ/RXRα异二聚体与PPRE序列的结合。这些结果表明，HSL基因受PPAR-γ/RXRα异二聚体转录调控，提示HSL基因表达受顺式作用元件调控。(C)2006 Elsevier Inc.保留所有权利。
Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step of lipolysis in adipose tissue. Several studies suggest that protein phosphorylation regulates the HSL enzymatic activity. On the other hand, the precise mechanism of the transcriptional regulation of the HSL gene remains to be elucidated. Here, we identified a functional peroxisome-proliferator responsive element (PPRE) in the mouse HSL promoter by reporter assay in CV-1 cells using serial deletion and point mutants of the 5'-flanking region. Chromatin immunoprecipitation (ChIP) analysis revealed that both peroxisome-proliferator activated receptor (PPAR gamma) and retinoid X receptor (RXR alpha) interacted with the region. Binding of the PPAR gamma/RXR alpha heterodimer to the PPRE sequence was also confirmed by electrophoretic mobility shift assay. These results indicate that the HSL gene is transcriptionally regulated by PPAR gamma/RXR alpha heterodimer, and suggest that a cis-acting element regulates the HSL gene expression. (c) 2006 Elsevier Inc. All rights reserved.