Lachinani Liana, Ghaedi Kamran, Tanhaei Somayeh, Salamian Ahmad, Karamali Fereshteh, Kiani-Esfahani Abbas, Rabiee Farzaneh, Yaghmaei Parichehreh, Baharvand Hossein, Nasr-Esfahani Mohammad Hossein
Department of Cell and Molecular Biology, Cell Science Research Center, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran.
Avicenna J Med Biotechnol. 2012 Oct;4(4):160-9.
Peroxisome Proliferator Activated Receptor gamma (PPARγ), a member of nuclear receptor superfamily, comprises two isoforms in mouse. These two isoforms are encoded by different mRNAs, which are arisen by alternative promoter usage. There are two promoter regions upstream of PPARγ gene. A 3 kb fragment, containing several transcription factor binding sites, acts as PPARγ1 promoter region. Thus, expression pattern of PPARγ1 isoform is due to the potential transcription factors that could influence its promoter activity. PPARγ, Retinoid X Receptor (RXR) and Vitamin D Receptor (VDR), as nuclear receptors could influence PPARγ gene expression pattern during several differentiation processes. During neural differentiation, PPARγ1 isoform expression reaches to maximal level at neural precursor cell formation.
A vast computational analysis was carried out to reveal the PPARγ1 promoter region. The putative promoter region was then subcloned upstream of an EGFP reporter gene. Then the functionality of PPARγ1 promoter was assessed in different cell lines.
Results indicated that Rosiglitazone increased PPARγ1 promoter regulated EGFP expression of neural precursor cells during Embryoid Body (EB) formation. Furthermore vitamin D reduced PPARγ1 promoter regulated EGFP expression of neural precursor cells during EB formation through binding to its receptor.
This study suggests that there are potential response elements for PPAR/RXR and VDR/RXR heterodimers in PPARγ1 isoform promoter. Also VDR/RXR heterodimers may decrease PPARγ expression through binding to its promoter.
过氧化物酶体增殖物激活受体γ（PPARγ）是核受体超家族的成员，在小鼠中包含两种亚型。这两种亚型由不同的mRNA编码，这些mRNA通过选择性启动子的使用而产生。PPARγ基因上游有两个启动子区域。一个包含多个转录因子结合位点的3 kb片段作为PPARγ1启动子区域。因此，PPARγ1亚型的表达模式归因于可能影响其启动子活性的潜在转录因子。PPARγ、视黄酸X受体（RXR）和维生素D受体（VDR）作为核受体，在几个分化过程中可能影响PPARγ基因的表达模式。在神经分化过程中，PPARγ1亚型的表达在神经前体细胞形成时达到最高水平。
进行了大量的计算分析以揭示PPARγ1启动子区域。然后将推定的启动子区域亚克隆到增强绿色荧光蛋白（EGFP）报告基因的上游。然后在不同的细胞系中评估PPARγ1启动子的功能。
结果表明，罗格列酮在胚状体（EB）形成过程中增加了PPARγ1启动子调节的神经前体细胞的EGFP表达。此外，维生素D在EB形成过程中通过与其受体结合降低了PPARγ1启动子调节的神经前体细胞的EGFP表达。
本研究表明，PPARγ1亚型启动子中存在PPAR/RXR和VDR/RXR异二聚体的潜在反应元件。此外，VDR/RXR异二聚体可能通过与其启动子结合而降低PPARγ的表达。
