THE T-BOX NEAR THE ZINC FINGERS OF THE HUMAN VITAMIN-D-RECEPTOR IS REQUIRED FOR HETERODIMERIC DNA-BINDING AND TRANSACTIVATION

The T-box mediates binding of retinoid X receptor (RXR) homodimers to DNA while the P- and D-box in the zinc fingers of steroid hormone rece ptors play roles in DNA-binding specificity and homodimerization, resp ectively. We investigated the function of these elements in the human vitamin D receptor (hVDR) by mutating a Lys-Glu pair of amino acids in the T-box, and by altering the P- and D-boxes to the corresponding re sidues of the glucocorticoid receptor (GR). The T-box mutant hVDR disp layed attenuated vitamin D responsive element (VDRE) binding in the pr esence of RXR and was severely compromised in transcriptional activati on. In contrast, GR P/D-box mutant hVDRs bound to the rat osteocalcin VDRE and elicited near normal transcriptional activation. The T-box mu tant uniquely exhibited dominant negative properties, highlighting the significance of this region of hVDR for heterodimeric transcriptional activation. (C) 1995 Academic Press, Inc.