GSBS Student Publications
Title
Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene
GSBS Program
Biochemistry & Molecular Pharmacology
Publication Date
2001-02-17
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1016/S0039-128X(00)00160-4
Source
Steroids. 2001 Mar-May;66(3-5):159-70.
Journal/Book/Conference Title
Steroids
Related Resources
PubMed ID
11179723
Repository Citation
Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; Montecino, Martin; Van Wijnen, Andre J.; Javed, Amjad; and Gutierrez, Soraya E., "Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene" (2001). GSBS Student Publications. 694.
https://escholarship.umassmed.edu/gsbs_sp/694