Control of nuclear transcription of vitamin D-dependent genes by vitamin D.

Abstract

Vitamin D acts on the genome via its active metabolite, calcitriol, which is bound to its nuclear receptor (vitamin D receptor) and a DNA response element. The characterization of the DNA target of the vitamin D receptor in vitamin D-activated or -repressed genes and structure-function analysis of the vitamin D receptor have led to several advances. These include a better understanding of the mechanisms of transactivation via the vitamin D receptor by the description of direct and indirect interactions of the vitamin D receptor with the basal transcriptional machinery. Physiological evidence for heterodimerization of the vitamin D receptor with the retinoid X receptor, and with other liganded or unliganded nuclear receptors, has indicated how the genetic response to vitamin D can be modulated. This modulation can also be brought about by cooperation between vitamin D receptor and transcription factors, by the action of a dominant negative isoform of vitamin D receptor, and by cross-talk between the signalling pathways for vitamin D and growth factors. These new concepts, plus the development of analogues of calcitriol, all indicate considerable progress towards vitamin D therapy for several disorders, including renal diseases.