Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional 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 regulating physiologic responsiveness of vitamin D-dependent genes in bone cells. We briefly review factors which contribute to vitamin D transcriptional control. The organization of the vitamin D response element (VDRE), the multiple activities of the vitamin D receptor transactivation complex, and the necessity for protein-protein interactions between the VDR-RXR heterodimer activation complex and DNA binding proteins at other regulatory elements, including AP-1 sites and TATA boxes, provide for precise regulation of gene activity 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 nuclear architecture. Modifications in nucleosomal organization, DNase I hypersensitivity and localization of vitamin D receptor interacting proteins in subnuclear domains are regulatory components of vitamin D-dependent gene transcription. A model is proposed to account for the inability of vitamin D induction of the osteocalcin gene in the absence of ongoing basal transcription by competition of the YY1 nuclear matrix-associated transcription factor for TFIIB-VDR interactions. Activation of the VDR-RXR complex at the OC VDRE occurs through modifications in chromatin mediated in part by interaction of OC gene regulatory sequences with the nuclear matrix-associated Cbfa1 (Runx2) transcription factor which is required for osteogenesis.
Lian
J B
JB
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655-1016, USA. Jane.Lian@umassmed.edu
Stein
J L
JL
Stein
G S
GS
Montecino
M
M
van Wijnen
A J
AJ
Javed
A
A
Gutierrez
S
S
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure*; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D015675:Osteocalcin / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014807:Vitamin D / Q000494:pharmacology*
D002843:Chromatin; D015675:Osteocalcin; D014807:Vitamin D