Zinc increases the activity of vitamin D-dependent promoters in osteoblasts

Zinc modulates the structure and binding of the DNA binding domain of the 1 alpha,25-dihydroxyvitamin D-3 receptor to specific vitamin D response elem ent DNA (Nature Biotechnology 16, 262-266, 1998). To determine whether zinc alters 1 alpha,25-dihydroxyvitamin D-3-regulated genes in cells, we perman ently transfected rat osteoblasts with two vitamin D-dependent promoter-rep orter systems and examined their responses to 1 alpha,25-dihydroxyvitamin D -3 in the presence of increasing amounts of extracellular zinc. When extrac ellular zinc concentrations were increased in the presence of 1 alpha,25-di hydroxyvitamin D-3, there was an increase in the activity of 1 alpha,25-dih ydroxyvitamin D-3-dependent promoters with increasing concentrations of zin c. The effect was specific for zinc since metals such as copper failed to i ncrease the activity of 1 alpha,25-dihydroxyvitamin D-3-dependent promoters . The concentration of the vitamin D receptor within the cell and the affin ity of 1 alpha,25-dihydroxyvitamin D-3 for its receptor remained unchanged with added zinc. Our results show that zinc increases the activity of 1 alp ha,25-dihydroxyvitamin D-3-dependent promoters in osteoblasts. (C) 2000 Aca demic Press.