9-cis-Retinoic acid represses estrogen-induced expression of the very low density apolipoprotein II gene

Abstract The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9- cis -retinoic acid (9- cis -RA) in the activation of the apoVLDLII promoter. We first concentrated on a potential RXR recognition site, which deviates at only one position from a perfect direct A/GGGTCA repeat spaced by one nucleotide (DR-1) and was earlier identified as a common HNF-4/COUP-TF ecognition site. However, band shift analysis revealed that this imperfect DR-1 motif does not interact with RXRα-homodimers. In accordance with this observation we found that this regulatory element does not mediate transactivation through RXRα in the presence of 9- cis -RA. However, our experiments revealed another, unexpected, effect of 9- cis -RA. Instead of stimulating, 9- cis -RA attenuated estrogen-induced expression of transfected estrogenresponsive VLDL-CAT reporter plasmids. This repression appeared to take place through the main estrogen response element (ERE) of the gene. Importantly, 9- cis -RA also strongly repressed the estrogen-induced expression of the endogenous apoVLDLII gene in cultured chicken hepatoma cells.