Regulation of the Bone-Specific Osteocalcin Gene by p300 Requires Runx2/Cbfa1 and the Vitamin D3 Receptor but Not p300 Intrinsic Histone Acetyltransferase Activity

• DOI: 10.1128/mcb.23.9.3339-3351.2003
• Publication Date: 2003-04-16T17:24:16Z
• Authors: Jose Sierra; Alejandro Villagra; Roberto Paredes; Fernando Cruzat; Soraya Gutierrez; Amjad Javed; Gloria Arriagada; Juan Olate; Maria Imschenetzky; Andre J. van Wijnen; Jane B. Lian; Gary S. Stein; Janet L. Stein; Martin Montecino
• Keywords: Chromatin immunoprecipitation; Histone acetyltransferase; P300-CBP Transcription Factors

p300 is a multifunctional transcriptional coactivator that serves as an adapter for several transcription factors including nuclear steroid hormone receptors. possesses intrinsic histone acetyltransferase (HAT) activity may be critical promoting steroid-dependent activation. In osteoblastic cells, of the bone-specific osteocalcin (OC) gene principally regulated by Runx2/Cbfa1 factor and stimulated in response to vitamin D(3) via receptor complex. Therefore, we addressed control basal D(3)-enhanced OC promoter. We find transient overexpression results significant dose-dependent increase both D(3)-stimulated activity. This stimulatory effect requires intact binding sites D-responsive element. addition, coimmunoprecipitation, show endogenous proteins are components same complexes within cells under physiological concentrations. also demonstrate chromatin immunoprecipitation assays p300, Runx2/Cbfa1, 1alpha,25-dihydroxyvitamin interact with promoter expressing this gene. The on independent its HAT activity, HAT-deficient mutant protein up-regulates expression cooperates P/CAF extent wild-type p300. On basis these results, propose interacts key regulators bridges distal proximal sequences facilitate responsiveness D(3).