The Carbonic Anhydrase II (CAII) gene that encodes an enzyme involved in proton production is expressed in several cell types including monocyte/macrophage-derived osteoclasts. We have analyzed the regulation of the chicken CAII promoter/reporter construct by nuclear hormone receptors of the VDR subfamily in HD11 avian macrophages. The CAII expression is stimulated by 1, 25-dihydroxyvitamin D(3) but not by 9-cis retinoic acid and repressed by VDR overexpression due to RXR squelching. It is also stimulated by all-trans retinoic acid only when RARalpha is overexpressed, and is dependent on a RARE located in the distal part of the promoter and bound by RARalpha homodimer. Finally, in macrophages, unlike in erythrocytes, the CAII promoter is unresponsive to thyroid hormone. Our results demonstrate the first retinoic acid response element in the CAII promoter and show that according to cell type, different nuclear receptors of the VDR subfamily can regulate the CAII gene.
Copyright 2000 Academic Press.