Opposite Regulation of the Human Apolipoprotein M Gene by Hepatocyte Nuclear Factor 1 and Jun Transcription Factors
| Autor: | Dimitris Kardassis, Ioanna Mosialou, Konstantin Krasagakis |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Transcriptional Activation
Apolipoprotein B Proto-Oncogene Proteins c-jun JUNB Apolipoproteins M Models Biological Biochemistry Cell Line Transactivation Phorbol Esters Humans Gene Regulation Promoter Regions Genetic Molecular Biology Transcription factor Inflammation Regulation of gene expression biology Cholesterol HDL Cell Biology Molecular biology Lipocalins Transcription Factor AP-1 Hepatocyte nuclear factors AP-1 transcription factor Apolipoproteins APOM Gene Expression Regulation Hepatocyte Nuclear Factor 1 Mutation biology.protein |
| Zdroj: | Journal of Biological Chemistry. 286:17259-17269 |
| ISSN: | 0021-9258 |
| Popis: | HDL is a negative risk factor for atherosclerosis because of its multiple atheroprotective functions. Inflammation converts HDL particles from anti-atherogenic to pro-atherogenic, and this transformation is associated with changes in HDL structure and composition. Apolipoprotein M (apoM) has been recently shown to play a role in the maturation of HDL in plasma and to protect from atherosclerosis. ApoM gene is expressed primarily in the liver and kidney and is down-regulated by pro-inflammatory signals. We now show that the human apoM promoter harbors a dual specificity regulatory element in the proximal region that binds hepatocyte nuclear factor 1 (HNF-1) and members of the AP-1 family of pro-inflammatory transcription factors (c-Jun and JunB). Overexpression of c-Jun or JunB repressed both the basal and the HNF-1-mediated transactivation of the human apoM promoter. Treatment of HepG2 cells with potent inflammation-inducing phorbol esters or overexpression of PKCα was associated with a marked inhibition of apoM gene expression in a c-Jun/JunB-dependent manner. We provide evidence for a novel mechanism of inflammation-induced transcriptional repression that is based on the competition between HNF-1 and Jun proteins for binding to the same regulatory region. A similar mechanism accounts for the down-regulation of the liver-specific apolipoprotein A-II gene by Jun factors. Our studies provide novel insights on the mechanisms that control the expression of liver-specific apolipoprotein genes during inflammation and could affect the maturation and the functionality of HDL particles. |
| Databáze: | OpenAIRE |
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