Chromatin hyperacetylation abrogates vitamin D-mediated transcriptional upregulation of the tissue-specific osteocalcin gene in vivo

Biochemistry. 1999 Jan 26;38(4):1338-45. doi: 10.1021/bi982171a.


Cells expressing the bone-specific osteocalcin (OC) gene exhibit two DNase I hypersensitive sites within the proximal (nt -170 to -70) and distal (nt -600 to -400) promoter. These sites overlap elements that independently or in combination contribute to basal and vitamin D-stimulated OC gene transcription. Here we address mechanisms that participate in control of chromatin remodelling at these sites. By applying nuclease digestion and indirect end-labeling or by combining intranuclear footprinting and ligation-mediated PCR, we investigated the effects of nuclear protein hyperacetylation on both chromatin organization and transcriptional activation of the OC gene in bone-derived cells. We report that chromatin hyperacetylation blocks vitamin D stimulation of OC transcription and prevents a key transition in the chromatin structure of the OC gene which is required for formation of the distal DNase I hypersensitive site. This transition involves interaction of sequence-specific nuclear factors and may be required for the ligand-dependent binding of the vitamin D receptor complex, which results in transcriptional enhancement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Bone and Bones / metabolism
  • Butyrates / pharmacology
  • Calcitriol / pharmacology*
  • Chromatin / drug effects
  • Chromatin / genetics
  • Chromatin / metabolism*
  • DNA Footprinting
  • Deoxyribonuclease I
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Nuclear Proteins / metabolism
  • Osteocalcin / genetics*
  • Osteosarcoma
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / drug effects
  • Rats
  • Restriction Mapping
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology*
  • Transcriptional Activation / drug effects
  • Tumor Cells, Cultured


  • Butyrates
  • Chromatin
  • Nuclear Proteins
  • Osteocalcin
  • Deoxyribonuclease I
  • Calcitriol