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

Martin Montecino, Baruch Frenkel, André J. Van Wijnen, Jane B. Lian, Gary S. Stein, Janet L. Stein

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36 Scopus citations

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 languageEnglish (US)
Pages (from-to)1338-1345
Number of pages8
JournalBiochemistry
Volume38
Issue number4
DOIs
StatePublished - Jan 26 1999

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Montecino, M., Frenkel, B., Van Wijnen, A. J., Lian, J. B., Stein, G. S., & Stein, J. L. (1999). Chromatin hyperacetylation abrogates vitamin D-mediated transcriptional upregulation of the tissue-specific osteocalcin gene in vivo. Biochemistry, 38(4), 1338-1345. https://doi.org/10.1021/bi982171a