| Autor: |
Raspè, Eric, Mautino, Gisèle, Duval, Caroline, Fontaine, Coralie, Duez, Hélène, Barbier, Olivier, Monte, Didier, Fruchart, Jamila, Fruchart, Jean-Charles, Staels, Bart |
| Zdroj: |
Journal of Biological Chemistry; December 2002, Vol. 277 Issue: 51 p49275-49281, 7p |
| Abstrakt: |
The Rev-erb and retinoic acid-related orphan receptors (ROR) are two related families of orphan nuclear receptors that recognize similar response elements but have opposite effects on transcription. Recently, the Rev-erbαgene promoter has been characterized and shown to harbor a functional Rev-erbα-binding site known as Rev-DR2, responsible for negative feedback down-regulation of promoter activity by Rev-erbα itself. The present study aimed to investigate whether Rev-erbαgene expression is regulated by RORα. Gel shift analysis demonstrated thatin vitrotranslated hRORα1 protein binds to the Rev-DR2 site, both as monomer and dimer. Chromatin immunoprecipitation assays demonstrated that binding of RORα to this site also occurred in vivoin human hepatoma HepG2 cells. The Rev-DR2 site was further shown to be functional as it conferred hRORα1 responsiveness to a heterologous promoter and to the natural human Rev-erbαgene promoter in these cells. Mutation of this site in the context of the natural Rev-erbαgene promoter abolished its activation by RORα, indicating that this site plays a key role in hRORα1 action. Finally, adenoviral overexpression of hRORα1 in HepG2 cells led to enhanced hRev-erbα mRNA accumulation, further confirming the physiological importance of RORα1 in the regulation of Rev-erbα expression. |
| Databáze: |
Supplemental Index |
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