Interaction of the 1α,25-dihydroxyvitamin D3 receptor at the distal promoter region of the bone-specific osteocalcin gene requires nucleosomal remodelling

Roberto Paredes, José Gutiérrez, Soraya Gutierrez, Lizabeth Allison, Marcia Puchi, Maria Imschenetzky, Andre Van Wijnen, Jane Lian, Gary Stein, Janet Stein, Martin Montecino

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36 Scopus citations

Abstract

1α,25-Dihydroxyvitamin D3-mediated transcriptional control of the bone-specific osteocalcin (OC) gene requires the integration of regulatory signals at the vitamin D-responsive element (VDRE) and flanking tissue-specific sequences. The 1α25-dihydroxyvitamin D3 receptor (VDR) is a member of the nuclear receptor superfamily and forms a heterodimeric complex with the receptor for 9-cis retinoic acid (RXR) that binds to the VDRE sequence. We have demonstrated previously that changes in chromatin structure at the VDRE region of the rat OC gene promoter accompany transcriptional enhancement in vivo, suggesting a requirement for chromatin remodelling. Here we show that the VDRE in the distal region of the OC gene promoter is refractory to binding of the VDR-RXR complex when organized in a nucleosomal context. Addition of the ligand 1α,25-dihydroxyvitamin D3 or the presence of other transcription factors, such as YY1 and Runx/Cbfa (core-binding factor α), which also bind to sequences partially overlapping or near the VDRE, is not sufficient to render the VDRE accessible. Thus the VDRRXR, unlike other steroid receptors, such as glucocorticoid receptor, progesterone receptor and thyroid receptor, is unable to bind its target sequence within a nucleosomal context. Taken together these results demonstrate that nucleosomal remodelling is required for in vivo occupancy of binding sites in the distal region of the OC gene promoter by the regulatory factors responsible for 1α,25-dihydroxyvitamin D3-dependent enhancement of transcription.

Original languageEnglish (US)
Pages (from-to)667-676
Number of pages10
JournalBiochemical Journal
Volume363
Issue number3
DOIs
StatePublished - May 1 2002

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Keywords

  • Chromatin structure
  • Transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Paredes, R., Gutiérrez, J., Gutierrez, S., Allison, L., Puchi, M., Imschenetzky, M., Van Wijnen, A., Lian, J., Stein, G., Stein, J., & Montecino, M. (2002). Interaction of the 1α,25-dihydroxyvitamin D3 receptor at the distal promoter region of the bone-specific osteocalcin gene requires nucleosomal remodelling. Biochemical Journal, 363(3), 667-676. https://doi.org/10.1042/0264-6021:3630667