Interaction of vitamin D and retinoid receptors on regulation of gene expression

Abstract

Vitamin D and retinoic acid (RA) receptors (VDRs and RARs, respectively), bind as heterodimers with the retinoid X receptor (RXR) to hormone response elements (HREs) in target genes. In some cases RA and vitamin D can cooperate to stimulate transcription through the same HRE. However, VDR/RXR heterodimers bind in a transcriptionally unproductive manner and without a defined polarity on certain RA response elements, and under these circumstances vitamin D inhibits the response to RA. Although competition for binding to DNA may contribute to this inhibitory response, titration of common coactivators by VDR also appears to be involved in transrepression. Therefore, the transcriptional response to RA and vitamin D depends on a complex combinatory pattern of interaction among different receptors wih DNA and coactivators.