de-novo identification of pparγrxr binding sites and direct targets during adipogenesis新创的识别pparγrxr结合位点在脂肪生成和直接目标.pdfVIP

De-Novo Identification of PPARc/RXR Binding Sites and Direct Targets during Adipogenesis 1. 1,2. 1 1 Mohamed Sabry Hamza , Sebastian Pott , Vinsensius B. Vega , Jane S. Thomsen , Gopalan 1 1 1 1,2 1 Srinivasan Kandhadayar , Patrick Wei Pern Ng , Kuo Ping Chiu , Sven Pettersson , Chia Lin Wei , Yijun 1 1 Ruan , Edison T. Liu * 1 Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore, 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden Abstract Background: The pathophysiology of obesity and type 2 diabetes mellitus is associated with abnormalities in endocrine signaling in adipose tissue and one of the key signaling affectors operative in these disorders is the nuclear hormone transcription factor peroxisome proliferator-activated receptor-c (PPARc). PPARc has pleiotropic functions affecting a wide range of fundamental biological processes including the regulation of genes that modulate insulin sensitivity, adipocyte differentiation, inflammation and atherosclerosis. To date, only a limited number of direct targets for PPARc have been identified through research using the well established pre-adipogenic cell line, 3T3-L1. In order to obtain a genome-wide view of PPARc binding sites, we applied the pair end-tagging technology (ChIP-PET) to map PPARc binding sites in 3T3-L1 preadipocyte cells. Methodology/Principal Findings: Coupling gene expression profile analysis with ChIP-PET, we identified in a ge