GSBS Student Publications

Title

YY1 regulates vitamin D receptor/retinoid X receptor mediated transactivation of the vitamin D responsive osteocalcin gene

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

1997-01-07

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology; Department of Cell Biology; Howard Hughes Medical Institute, Program in Molecular Medicine

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The responsiveness of genes to steroid hormones is principally mediated by functional interactions between DNA-bound hormone receptors and components of the transcriptional initiation machinery, including TATA-binding protein, TFIIB, or other RNA polymerase II associated factors. This interaction can be physiologically modulated by promoter context-specific transcription factors to facilitate optimal responsiveness of gene expression to hormone stimulation. One postulated regulatory mechanism involves the functional antagonism between hormone receptors and nonreceptor transcription factors interacting at the same hormone response element. Here we demonstrate that the multifunctional regulator YY1 represses 1,25-dihydroxyvitamin D3 (vitamin D)-induced transactivation of the bone tissue-specific osteocalcin gene. We identify YY1 recognition sequences within the vitamin D response element (VDRE) of the osteocalcin gene that are critical for YY1-dependent repression of vitamin D-enhanced promoter activity. We show that YY1 and vitamin D receptor (VDR)/retinoid X receptor heterodimers compete for binding at the osteocalcin VDRE. In addition, we find that YY1 interacts directly with TFIIB, and that one of the two tandemly repeated polypeptide regions of TFIIB spanning the basic domain is responsible for this interaction. TFIIB and VDR can also interact directly, and these factors synergize to mediate transactivation. Our results suggest that YY1 regulates vitamin D enhancement of osteocalcin gene transcription in vivo by interfering with the interactions of the VDR with both the VDRE and TFIIB.

Source

Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):121-6.

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to article in PubMed

PubMed ID

8990171

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