vitamin D response element
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Vitamin D response element (VDRE) is a type of DNA sequence that is found in the promoter region of
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
regulated genes. This sequence binds the
vitamin D receptor The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodim ...
(VDR), when complexed with
calcitriol Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
(1,25(OH)2D), the active form of vitamin D, and so regulates the expression of many genes. These
response element Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes. Under conditions of stress, a transcription activator protein binds ...
s typically consist of two conserved hexameric half-sites separated by a three nucleotide spacer, referred to as a DR3 (for direct repeat spaced by 3 type element). The sequence of a VDRE can have a strong influence on the degree of protein binding, particularly at the fifth position in the half-site, and many studies have focused on synthetic variations of response elements and not naturally occurring sequences. The VDR is widely distributed in tissues, and is not restricted to those tissues considered the classic targets of vitamin D. The VDR upon binding to 1,25(OH)2D heterodimerizes with other nuclear hormone receptors, in particular the family of
retinoid X receptor The retinoid X receptor (RXR) is a type of nuclear receptor that is activated by 9-cis retinoic acid, which is discussed controversially to be of endogenous relevance, and 9-''cis''-13,14-dihydroretinoic acid, which is likely to be the major e ...
s. This VDR/RXR heterodimer complex binds to the specific VDRE in the promoters of genes which it regulates. A variety of additional proteins called coactivators complex with the activated VDR/RXR heterodimers either to form a bridge from the VDR/RXR complex binding to the VDRE to the proteins responsible for transcription such as RNA polymerase II binding to the transcription start site or to help unravel the chromatin at the site of the gene via recruitment of histone acetyl transferases (HAT), allowing transcription to proceed.


References

{{Reflist Vitamin D