Abstract
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.
Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
MeSH terms
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Animals
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Blotting, Western
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CHO Cells
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Chromatin Immunoprecipitation
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Cricetinae
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Cricetulus
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Forkhead Box Protein O1
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism*
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Hep G2 Cells
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Humans
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Insulin / pharmacology
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Liver X Receptors
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Luciferases / genetics
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Luciferases / metabolism
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Mice
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Mutation
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Orphan Nuclear Receptors / genetics
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Orphan Nuclear Receptors / metabolism*
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Promoter Regions, Genetic / genetics*
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Protein Binding
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Response Elements / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Sterol Regulatory Element Binding Protein 1 / genetics
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Sterol Regulatory Element Binding Protein 1 / metabolism*
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Transcriptional Activation / drug effects
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Transfection
Substances
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FOXO1 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Insulin
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Liver X Receptors
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NR1H3 protein, human
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Nr1h3 protein, mouse
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Orphan Nuclear Receptors
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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Luciferases