Contributions of nuclear architecture and chromatin to vitamin D-dependenttranscriptional control of the rat osteocalcin gene

The vitamin D response element in the bone tissue-specific osteocalcin gene has served as a prototype for understanding molecular mechanisms regulatin g physiologic responsiveness of vitamin D-dependent genes in bone cells. We briefly review factors which contribute to vitamin D transcriptional contr ol. The organization of the vitamin D response element (VDRE), the multiple activities of the vitamin D receptor transactivation complex, and the nece ssity for protein-protein interactions between the VDR-RXR heterodimer acti vation complex and DNA binding proteins at other regulatory elements, inclu ding AP-1 sites and TATA boxes, provide for precise regulation of gene acti vity in concert with basal levels of transcription. We present evidence for molecular mechanisms regulating vitamin D-dependent mediated transcription of the osteocalcin gene that involve chromatin structure of the gene and n uclear architecture. Modifications in nucleosomal organization, DNase I hyp ersensitivity and localization of vitamin D receptor interacting proteins i n subnuclear domains are regulatory components of vitamin D-dependent gene transcription. A model is proposed to account fur the inability of vitamin D induction of the osteocalcin gene in the absence of ongoing basal transcr iption by competition of the YY1 nuclear matrix-associated transcription fa ctor for TFIIB-VDR interactions. Activation of the VDR-RXR complex at the O C VDRE occurs through modifications in chromatin mediated in part by intera ction of OC gene regulatory sequences with the nuclear matrix-associated Cb fa1 (Runx2) transcription factor which is required for osteogenesis. (C) 20 01 Elsevier Science Inc. All rights reserved.