All natural DR3-type vitamin D response elements show a similar functionality in vitro

• DOI: 10.1042/bj3520301
• Publication Date: 2015-08-10T22:13:13Z
• Authors: Andrea TOELL; Patsie POLLY; Carsten CARLBERG
• Keywords: Retinoid X receptor; Corepressor

The vitamin D3 receptor (VDR), which is the nuclear for 1α,25-dihydroxyvitamin [1α,25(OH)2D3], acts primarily as a heterodimer with retinoid X (RXR) and binds preferentially to directly repeated arrangements of two hexameric binding sites three spacing nucleotides [DR3-type D response elements (VDREs)]. In this study, all presently known natural DR3-type VDREs have been compared classified on basis their complex-formation VDR–RXR heterodimers ability stabilize conformations. Based affinity each VDRE heterodimers, were divided into classes. ligand sensitivity conformational stabilization was determined be in range 0.1nM. No significant differences 1α,25(OH)2D3-modulated interactions VDRE-complexed co-activator SRC-1 (steroid co-activator-1) or co-repressor NCoR (nuclear co-repressor) found. Taken together, appears major discriminating parameter between VDREs. This will not only facilitate further investigation principles DR3-type-VDRE-mediated gene regulation, but also strongly suggests that alone cannot explain pleiotropic genomic action 1α,25(OH)2D3.