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 LXR alpha-mediated elevated transcription by SREBP-1c promoter. Electrophoretic mobility shift assay and chromatin immuno-precipitation further suggested the ability of FoxO1 to inhibit LXR alpha binding with the LXRE in the SREBP-c promoter. FoxO1-mediated suppression of SREBP-1c promoter activity could be partially alleviated by insulin. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.