GSBS Student Publications
Title
1alpha,25-dihydroxy vitamin D3-enhanced expression of the osteocalcin gene involves increased promoter occupancy of basal transcription regulators and gradual recruitment of the 1alpha,25-dihydroxy vitamin D3 receptor-SRC-1 coactivator complex
Publication Date
2007-09-06
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Binding of 1alpha,25-dihydroxy vitamin D(3) to the C-terminal ligand-binding domain (LBD) of its receptor (VDR) induces a conformational change that enables interaction of VDR with transcriptional coactivators such as members of the p160/SRC family or the DRIP (vitamin D receptor-interacting complex)/Mediator complex. These interactions are critical for VDR-mediated transcriptional enhancement of target genes. The p160/SRC members contain intrinsic histone acetyl transferase (HAT) activities that remodel chromatin at promoter regulatory regions, and the DRIP/Mediator complex may establish a molecular bridge between the VDR complex and the basal transcription machinery. Here, we have analyzed the rate of recruitment of these coactivators to the bone-specific osteocalcin (OC) gene in response to short and long exposures to 1alpha,25-dihydroxy vitamin D3. We report that in intact osteoblastic cells VDR, in association with SRC-1, rapidly binds to the OC promoter in response to the ligand. The recruitment of SRC-1 correlates with maximal transcriptional enhancement of the OC gene at 4 h and with increased histone acetylation at the OC promoter. In contrast to other 1alpha,25-dihydroxy vitamin D3-enhanced genes, binding of the DRIP205 subunit, which anchors the DRIP/Mediator complex to the VDR, is detected at the OC promoter only after several hours of incubation with 1alpha,25-dihydroxy vitamin D(3), concomitant with the release of SRC-1. Together, our results support a model where VDR preferentially recruits SRC-1 to enhance bone-specific OC gene transcription.
DOI of Published Version
10.1002/jcp.21267
Source
J Cell Physiol. 2008 Mar;214(3):740-9. Link to article on publisher's site
Journal/Book/Conference Title
Journal of cellular physiology
Related Resources
PubMed ID
17786964
Repository Citation
Carvallo, Loreto; Henriquez, Berta; Paredes, Roberto; Olate, Juan; Onate, Sergio; Van Wijnen, Andre J.; Lian, Jane B.; Stein, Gary S.; Stein, Janet L.; and Montecino, Martin A., "1alpha,25-dihydroxy vitamin D3-enhanced expression of the osteocalcin gene involves increased promoter occupancy of basal transcription regulators and gradual recruitment of the 1alpha,25-dihydroxy vitamin D3 receptor-SRC-1 coactivator complex" (2007). GSBS Student Publications. 1401.
https://escholarship.umassmed.edu/gsbs_sp/1401