Retinoid Receptors Regulate the Transcription of Pregnancy Specific Glycoprotein Genes

LÓPEZ-DÍAZ, F.; KORITSCHONER, N.; NORES, R.; PANZETTA, G.; BOCCO, J.L.

Iguazú

Congreso; XL Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2004

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Expression of PSG genes is increased upon differentiation of cytotrophoblast to syncytiotrophoblast by an unknown mechanism. Retinoid receptors, RXRa and RARa regulate the differentiation of cytotrophoblast, activating gene transcription mainly by a ligand-induced manner. In addition, they interact with Sp1, enhancing its binding to CACCC-boxes and therefore increasing the Sp1-mediated activation of genes lacking canonical RAREs. Here we show that endogenous PSG expression in trophoblast-derived cells is induced by 9-cis retinoic acid (9cRA). Moreover, RXRa, RARa and Testicular Receptor (TR)4 activates the PSG5 promoter, which is recognized through a composite RARE/CACCC motif by RXRa and TR4, thereby confirming the potential role of the RARE. Most importantly, RXRa activates the PSG5 promoter in a ligand-dependent or independent manner at different expression levels. Accordingly, RXRa enhances Sp1 binding to the CACCC-box, but increasing concentrations of RXRa impairs this interaction and the Sp1-mediated activation, independently of its own DNA binding. These results suggests that the RARE/CACCC motif can integrate different regulatory signals, being able of switching from a Sp1-inducible to a retinoid-responsive state, suggesting for the first time, a mechanism explaining how is reached the high expression of PSG genes during trophoblast differentiation.