FoxO1 represses LXRα-mediated transcriptional activity of SREBP-1c promoter in HepG2 cells.
Recent studies have demonstrated that FoxO1 modulates the expression of SREBP-1c, but the exact mechanism remains unknown. Our results demonstrate that FoxO1 suppresses the SREBP-1c promoter transcriptional activity in HepG2 cells. This repression was independent of FoxO1 binding to the SREBP-1c promoter, but LXR responsive elements (LXREs) were crucial to this phenomenon. Moreover, FoxO1 also strongly inhibited the LXRα-mediated elevated transcription by SREBP-1c promoter. Electrophoretic mobility shift assay and chromatin immuno-precipitation further suggested the ability of FoxO1 to inhibit LXRα binding with the LXRE in the SREBP-1c promoter. FoxO1-mediated suppression of SREBP-1c promoter activity could be partially alleviated by insulin.
Liu
Xiaojun
X
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qiao
Aijun
A
Ke
Yaojun
Y
Kong
Xingxing
X
Liang
Jichao
J
Wang
Rui
R
Ouyang
Xiaoqing
X
Zuo
Ji
J
Chang
Yongsheng
Y
Fang
Fude
F
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D047369:Chromatin Immunoprecipitation; D006224:Cricetinae; D003412:Cricetulus; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D000071518:Liver X Receptors; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007328:Insulin; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D008156:Luciferases