YY1 represses vitamin D receptor-mediated 25-hydroxyvitamin D(3)24-hydroxylase transcription: relief of repression by CREB-binding protein

Mol Endocrinol. 2001 Jun;15(6):1035-46. doi: 10.1210/mend.15.6.0651.

Abstract

Ying Yang transcription factor (YY1) can repress or activate transcription. 25-Hydroxyvitamin D(3)-24-hydroxylase [24(OH)ase], an enzyme involved in the catabolism of 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], is up-regulated at the transcriptional level by 1,25-(OH)(2)D(3) to self-induce its deactivation. Here we report that YY1 can repress 1,25-(OH)(2)D(3)-induced 24(OH)ase transcription in CV1 cells transfected with vitamin D receptor (VDR) expression vector or in LLCPK(1) cells that contain VDR endogenously. With increasing amounts of YY1 DNA transfected (500 ng to 2 microg), ligand-dependent VDR activation of 24(OH)ase transcription was steadily repressed (maximum repression was 10-fold). Thus, YY1 may be a key modulator preventing activation at times that do not require the enzyme to be expressed. Relief of YY1 repression was observed in the presence of TFIIB or CBP (CREB binding protein) suggesting that YY1 may exert repression, in part, by sequestering TFIIB/CBP. Glutathione-S-transferase (GST) pull-down assays identified regions in the N and C termini of CBP that can bind YY1. In addition, the N-terminal region of CBP that interacts with YY1 can inhibit YY1 from binding to TFIIB. Thus, CBP may alleviate YY1-mediated repression, in part, by preventing YY1 from binding to TFIIB, which is required for VDR-mediated transcription. In summary, our results suggest that YY1 represses 24(OH)ase transcription, at least in part, by sequestering activator proteins involved in VDR-mediated transcription. In addition, our findings demonstrate a role for CBP in relief of repression of VDR-mediated transcription.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CREB-Binding Protein
  • Cell Line
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • Rats
  • Receptors, Calcitriol / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Steroid Hydroxylases / genetics*
  • Steroid Hydroxylases / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor TFIIB
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection
  • Vitamin D3 24-Hydroxylase
  • YY1 Transcription Factor

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Nuclear Proteins
  • Receptors, Calcitriol
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factor TFIIB
  • Transcription Factors
  • YY1 Transcription Factor
  • YY1 protein, human
  • Yy1 protein, rat
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • CREB-Binding Protein
  • CREBBP protein, human
  • Crebbp protein, rat