Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1338-1345 |
Number of pages | 8 |
Journal | Biochemistry |
Volume | 38 |
Issue number | 4 |
DOIs | |
State | Published - Jan 26 1999 |
ASJC Scopus subject areas
- Biochemistry