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 JB, Stein JL, Stein GS, Montecino M, Van Wijnen AJ, Javed A, Gutierrez SE. (2001). Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene. GSBS Student Publications. https://doi.org/10.1016/S0039-128X(00)00160-4. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/694