Retinoic acid , response element RARE

The form of vitamin A that is needed for regulating vitamin A-dependent gene expression is retinoic acid.All-fraws-retinoic acid can interact with each of the three RARs (RARa, RAR(3, and RARy) and each of the three RXRs (RXRa, RXR(3, and RXRy). 9-cX-Retinoic acid binds and effectively transactivates only the RXRs. The RARs and the RXRs recognize well-defined exacting response elements, termed retinoic acid response elements (RAREs) and retinoid X response elements (RXREs) that are present in the promoter regions of responsive genes. The RARs and RXRs bind to RAREs and/or RXREs as dimers, either homodimers or heterodimers. 

RAR-RXR heterodimer or RXR-RXR homodimer), the activated receptors bind with high affinity to the specific DNA retinoic acid response element (RARE) and effect mRNA transcription. Ultimately, the retinoid response is mediated by primary target genes, by interference with othertranscription factors or by control of certain posttranscriptional actions. 

These receptors, as heterodimers (RAR-RXR) or homodimers (RXR-RXR), function as RA-inducible transcriptional regulatory proteins by binding to DNA regions called retinoic acid response elements (RAREs) or retinoid X response elements (RXREs) located within the promoter of target genes. RAREs consist of direct repeats of the consensus half-site sequence AGGTCA separated most... 

Gene regulation and retinoic acid responsive elements (RAREs) 38... 

Vitamin A (retinol) is a fat-soluble vitamin important for the maintenance of skin, bone, and blood vessels, as well as for the promotion of vision (Theodosiou et al. 2010). It is obtained from the diet either as all-trans-retinol, retinyl esters, or P-carotene (Blomhoff and Blomhoff 2006) and is stored in the liver (Moise et al. 2007). Vitamin A is converted to retinoic acid (RA), which is formed mainly through intracellular oxidative metabolism by retinal dehydrogenases (RALDHs) (Lampen et al. 2000). RA plays important roles in embryonic development, organogenesis, tissue homeostasis, cell proliferation, differentiation, and apoptosis (Theodosiou et al. 2010). In adult mammals, RALDH is found in intestinal epithelial cells (lECs) and gut associated-dendritic cells (DCs) from Peyer s patches and mesenteric lymph nodes (Iwata 2004, Coombes et al. 2007). Gut-associated DCs and lECs can metabolize vitamin A to RA in vitro (Lampen 2000), which indicates they may be a source of RA in gut mucosa. RA binds to two families of nuclear receptors, RA receptor (RAR) isotypes (a, p, and y) and retinoic X receptor (RXR) isotypes (a, p, and y). RAR and RXR form heterodimers and interact with retinoic acid response elements (RAREs) within the promoters of retinoic acid responsive genes (Blomhoff and Blomhoff 2006). RAR is ubiquitously expressed and up-regulated by RA. RXR also... 

Both PML-RARa and PLZF-RARa can bind to a retinoic acid response element (RARE) as homodimers or, in combination with RXR, as multimeric complexes [115-117], and in comparison to the wild type RARa possess impaired transcriptional activities in response to ATRA [82, 83, 86, 116-118]. Expression of the PLZF-RARa protein in transgenic animals leads to the development of a myeloid leukaemia which, in contrast to PML-RARa transgenic mice, is resistant to ATRA [87]. Both PML-RARa and PLZF-RARa fusion proteins act as transcriptional repressors and are able to interact with RARa transcriptional co-repressors such as SMRT and N-CoR. However, unlike PML-RARa, PLZF-RARa can form, via its PLZF moiety, co-repressor complexes which are insensitive to ATRA [87, 107-110]. These data, for the... 

Dupe, V., Davenne, M., Brocard, J., Dolle, P., Mark, M., Dierich, A., Chambon, P., Rijli, F.M. 1997. In vivo functional analysis of the Hoxa-1 3 retinoic acid response element (3 RARE). Development 124, 399-410. 

Abbreviations used in this review APL, acute promyelocytic leukaemia CEF, chick embryo fibroblasts CRABP, cellular retinoic acid-binding protein ODC, ornithine decarboxylase RA, retinoic acid RARE, retinoic acid responsive element RAR, retinoic acid receptor RXR, retinoid X receptor TEMPO, 2,2,6,6-tetramethylpiperidine Y-oxide TOC, tracheal organ culture TPA, 12-<2-tetradecanoylphorbol-13-acetate TTNN, 6-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-naphthanoic acid TTNPB, 4-((.Q-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthyl)propenyl)benzoic acid. 

A FIGURE 11-42 Consensus sequences of DNA response elements that bind three nuclear receptors. The response elements for the glucocorticoid receptor (GRE) and estrogen receptor (ERE) contain inverted repeats that bind these homodimeric proteins. The response elements for heterodimeric receptors contain a common direct repeat separated by three to five base pairs, for the vitamin D3 receptor (VDRE), thyroid hormone receptor (TRE), and retinoic acid receptor (RARE). The repeat sequences are indicated by red arrows. [See K. Umesono etal., 1991, Ce//65 1255, and A. M. Naaretal., 1991, Ce//65 1267]... 

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