RGD Reference Report - Retinoids increase alpha-1 acid glycoprotein expression at the transcriptional level through two distinct DR1 retinoic acid responsive elements. - Rat Genome Database
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Retinoids increase alpha-1 acid glycoprotein expression at the transcriptional level through two distinct DR1 retinoic acid responsive elements.

Authors: Mouthiers, A  Mejdoubi, N  Baillet, A  Amelie, PA  Porquet, D 
Citation: Mouthiers A, etal., Biochim Biophys Acta. 2004 May 25;1678(2-3):135-44.
RGD ID: 2316642
Pubmed: (View Article at PubMed) PMID:15157739
DOI: Full-text: DOI:10.1016/j.bbaexp.2004.03.005

In the present study, we analyzed the influence of retinoic acids on the expression of alpha-1 acid glycoprotein (AGP). We show that in rat primary hepatocytes, 9-cis retinoic acid and all-trans retinoic acid increase AGP gene expression at the transcriptional level. Transient transfections of rat primary hepatocytes with a reporter construct driven by the rat AGP gene promoter indicated that retinoids regulate AGP gene expression via the -763/-138 region of the AGP promoter. Furthermore, cotransfection experiments with retinoic acid receptor alpha (RARalpha) and retinoid X receptor alpha (RXRalpha) expression vectors in NIH3T3 cells demonstrated that both RXRalpha/RXRalpha homodimer and RXRalpha/RARalpha heterodimer are competent for ligand-induced transactivation of the AGP promoter. Unilateral deletion and site-directed mutagenesis identified two retinoic-acid responsive elements (RARE), RARE-I and RARE-II, which interestingly correspond to a direct repeat of two TGACCT-related hexanucleotides separated by a single bp only (DR1-type response element). Cotransfection assays showed that RXRalpha and RARalpha activate AGP gene transcription through these two elements either as a homodimer (RXRalpha/RXRalpha) or as a heterodimer (RXRalpha/RARalpha). The RXRalpha/RXRalpha homodimer acts most efficiently through the RARE-I response element to promote AGP transactivation, whereas the RXRalpha/RARalpha heterodimer mediates transactivation better via the RARE-II responsive element.

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Genes (Rattus norvegicus)
Orm1  (orosomucoid 1)


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