Analysis of regulatory regions in the COL1A1 gene responsible for 1,25‐dihydroxyvitamin D3‐mediated transcriptional repression in osteoblastic cells

Dubravko Pavlin, Antonio Bedalov, Mark S. Kronenberg, Barbara E. Kream, David W. Rowe, Catharine L. Smith, J. Wesley Pike, Alexander C. Lichtler

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The synthesis of type 1 colagen in bone cells is inhibited by the calcium‐regulating hormone 1,25‐dihydroxyvitamin D3. Earlier work from our laboratoties has indicated that vitamin D regulation is at the level of transcription, based on result from both nuclear run‐off assays and functional analysis of a hybrid gene consisting of a 3.6 kb COL1A1 promoter fragment fused to the chloraphenicol acetyltransferase reporter gene. In the present study, we investigated the molecular basis for vitamin D‐mediated transcriptional repression of the COL1A1 gene and report the identification of a region within the COL1A1 upstream promoter (the Hindlll‐Pstl restriction fragment between nucleotides‐2295 and ‐1670) which is necessary for 1,25‐dihydroxyvitamin D3 responsiveness in osteoblastic cells. This hormone‐mediated inhibitory effect on the marker gene parallels the inhibition of the endogenous collagen gene. A 41 bp fragment from this region (between nucleotides‐2256 and ‐2216) contains a sequence which is very similar to vitamin D‐responsive elements identified in the osteocalcin gene. Estracts that binds specifically to this 41 bp fragment, as demonstrated by bandshift anslysis. However, deletion of this vitamin D receptor binding region from either a‐3.5 kb or a‐2.3 kb promoter fragment did not abolish vitamin D responsiveness. These results indicate that a vitamin D response element similar to that described for other D responsive genes (osteocalcin and osteopontin) does not alone mediate the repression of COL1A1 by 1,25‐dihydroxyvitamin D3.

Original languageEnglish (US)
Pages (from-to)490-501
Number of pages12
JournalJournal of Cellular Biochemistry
Volume56
Issue number4
DOIs
StatePublished - Dec 1994

Keywords

  • bone cells in culture
  • gene regulation by steroid hormone
  • nucleotides
  • type I collagen
  • vitamin D

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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