Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption. | ||||||||
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1Alpha,25(OH)2D3-induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter.Kim MS, Fujiki R, Murayama A, Kitagawa H, Yamaoka K, Yamamoto Y, Mihara M, Takeyama K, Kato S The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan. Although transactivation by the liganded vitamin D receptor (VDR) is well described at the molecular level, the precise molecular mechanism of negative regulation by the liganded VDR remains to be elucidated. We have previously reported a novel class of negative vitamin D response element (nVDRE) called 1alphanVDRE in the human 25(OH)D31alpha-hydroxylase [1alpha(OH)ase] gene by 1alpha,25(OH)2D3-bound VDR. This element was composed of two E-box-type motifs that bound to VDIR for transactivation, which was attenuated by liganded VDR. Here, we explore the possible functions of VDIR and E-box motifs in the human (h) PTH and hPTHrP gene promoters. Functional mapping of the hPTH and hPTHrP promoters identified E-box-type elements acting as nVDREs in both the hPTH promoter (hPTHnVDRE; -87 to -60 bp) and in the hPTHrP promoter (hPTHrPnVDRE; -850 to -600 bp; -463 to -104 bp) in a mouse renal tubule cell line. The hPTHnVDRE alone was enough to direct ligand-induced transrepression mediated through VDR/retinoid X receptor and VDIR. Direct DNA binding of hPTHnVDRE to VDIR, but not VDR/retinoid X receptor, was observed and ligand-induced transrepression was coupled with recruitment of VDR and histone deacetylase 2 (HDAC2) to the hPTH promoter. These results suggest that negative regulation of the hPTH gene by liganded VDR is mediated by VDIR directly binding to the E-box-type nVDRE at the promoter, together with recruitment of an HDAC corepressor for ligand-induced transrepression. Published 29 January 2007 in Mol Endocrinol, 21(2): 334-42.
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