Control of nuclear transcription of vitamin D-dependent genes by vitamin D.
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.
Perret
C
C
INSERM U129, Faculté Cochin, ICGM, Paris, France.
Colnot
S
S
Romagnolo
B
B
Thomasset
M
M
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology*
D006133:Growth Substances; D018167:Receptors, Calcitriol; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014807:Vitamin D; D004247:DNA; D002117:Calcitriol