Nakachi Yutaka, Yagi Ken, Nikaido Itoshi, Bono Hidemasa, Tonouchi Mio, Schönbach Christian, Okazaki Yasushi
Division of Functional Genomics & Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
Biochem Biophys Res Commun. 2008 Jul 25;372(2):362-6. doi: 10.1016/j.bbrc.2008.05.037. Epub 2008 May 19.
PPARgamma (peroxisome proliferator-activated receptor gamma) acts as a key molecule of adipocyte differentiation, and transactivates multiple target genes involved in lipid metabolic pathways. Identification of PPARgamma target genes will facilitate to predict the extent to which the drugs can affect and also to understand the molecular basis of lipid metabolism. Here, we have identified five target genes regulated directly by PPARgamma during adipocyte differentiation in 3T3-L1 cells using integrated analyses of ChIP-on-chip and expression microarray. We have confirmed the direct PPARgamma regulation of five genes by luciferase reporter assay in NIH-3T3 cells. Of these five genes Hp, Tmem143 and 1100001G20Rik are novel PPARgamma targets. We have also detected PPREs (PPAR response elements) sequences in the promoter region of the five genes computationally. Unexpectedly, most of the PPREs detected proved to be atypical, suggesting the existence of more atypical PPREs than previously thought in the promoter region of PPARgamma regulated genes.
过氧化物酶体增殖物激活受体γ（PPARγ）是脂肪细胞分化的关键分子，可反式激活多个参与脂质代谢途径的靶基因。鉴定PPARγ靶基因将有助于预测药物影响的程度，并有助于理解脂质代谢的分子基础。在此，我们通过芯片上的染色质免疫沉淀（ChIP-on-chip）和表达微阵列的综合分析，在3T3-L1细胞脂肪细胞分化过程中鉴定了五个由PPARγ直接调控的靶基因。我们通过在NIH-3T3细胞中进行荧光素酶报告基因检测，证实了PPARγ对五个基因的直接调控。在这五个基因中，Hp、Tmem143和1100001G20Rik是新的PPARγ靶标。我们还通过计算检测了这五个基因启动子区域中的PPAR反应元件（PPREs）序列。出乎意料的是，检测到的大多数PPREs被证明是非典型的，这表明在PPARγ调控基因的启动子区域中存在比以前认为的更多的非典型PPREs。
