Receptors response elements

Peroxisome Proliferator-Activated Receptors. Figure 3 Transcription of PPAR target genes. A schematic representation of the transcription of PPAR-regulated genes in the absence (a) and presence (b) of PPAR ligand. Abbreviations PPAR-RE, peroxisome proliferator-activated receptor-response element RNA Pol II, RNA polymerase II TATA-BP, TATA-binding protein. 

Chou WY, Stewart MJ, Kruijer W, Crabb DW. The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors. Arch Biochem Biophys 2000 280 192-200. 

Geick, A., Eichelbaum, M. and Burk, O. (2001) Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. Journal of Biological Chemistry, 276, 14581-14587. 

Figure 5.36 Mechanism of the receptor-mediated induction of CYP4A by a chemical such as the drug clofibrate. The inducer-receptor (PPAR) complex enters the nucleus, binds with RXR, and the complex binds to the receptor response elements in the CYP gene. This induces the production of CYP4A mRNA, which leads to the production of CYP4A protein and functional enzyme. Alternatively, the drug may perturb lipid metabolism leading to increases in a lipid(s), which will bind to the receptor and cause the same response. Abbreviations PPAR, peroxisome proliterator-activated receptor RXR, retinoid X receptor.

Dostert A, Heinzel T. Negative glucocorticoid receptor response elements and their role in glucocorticoid action. Curr Pharm Des. 2004 10 2807-2816. 

El-Sankary W, Bombail V, Gibson GG, Plant N (2002) Glucocorticoid-mediated induction of CYP3A4 is decreased by disruption of a protein DNA interaction distinct from the pregnane X receptor response element. Drug Metab Dispos 30, 1029-1034. 

A novel peroxisome proliferator-activated receptor responsive element-luciferase reporter mouse reveals gender specificity of peroxisome proliferator-activated receptor activity in liver. Mol Endocrinol. 21(2), 388-400. 

Lu, Y., Heydel, J. M., Li, X., Bratton, S., Lindblom, T., and Radominska-Pandya, A. (2005) Lithocholic acid decreases expression of UGT2B7 in Caco-2 cells a potential role for a negative farnesoid X receptor response element. Drug Metab. Dispos. 33, 937-946. 

To create xenobiotic receptor reporter transgenic mice that also express a luciferase reporter gene under the control of the xenobiotic receptor responsive elements. Such nuclear receptor reporter transgenic mice have been reported for a number of receptors, such as the estrogen receptor (ER) [85], famesoid X receptor (FXR) [86], and PPAR [87], These mice can be used to monitor the in vivo responses of these receptors to both xenobiotics and endobiotics. 

Ciana, P., Bisemi, A., Tatangelo, L., Tiveron, C., Sciarroni, A. R, Ottobrini, L., and Maggi, A. (2007) A novel peroxisome prohferator-activated receptor responsive element-luciferase reporter mouse reveals gender specificity of peroxisome prohferator-activated receptor activity in fiver. Mol. Endocrinol. 21, 388 400. 

Pascussi, J. M., Jounaidi, Y., Drocourt, L., Domergue, J., Balabaud, C., Maurel, P., and Vilarem, M. J. (1999) Evidence for the presence of a functional pregnane X receptor response element in the CYP3A7 promoter gene. Biochem. Biophys. Res. Commun. 260, 377-381. 

Pineda Torra, I., Jamshidi, Y., Flavell, D. M., Fruchart, J. C., and Staels, B. (2002) Characterization of the human PPARalpha promoter identification of a functional nuclear receptor response element. Mol. Endocrinol. 16, 1013-1028. 

Nuclear-Receptor Response Elements Contain Inverted or Direct Repeats... 

Some nuclear-receptor response elements, such as those for the receptors that bind vitamin D3, thyroid hormone, and retinoic acid, are direct repeats of the same sequence recognized by the estrogen receptor, separated by three to five base pairs (Figure ll-42c-e). The specificity for responding to these different hormones by binding distinct receptors Is determined by the spacing between the repeats. The receptors that bind to such direct-repeat response elements do so as heterodimers with a common nuclear-receptor monomer called RXR. The vitamin D3 response element, for example, Is bound by the RXR-VDR heterodimer. 

Fig. 6. Coordinated transcriptional regulation of fatty acid desaturases and elongases in mammals. PUFA, polyunsaturated fatty acids +, stimulation inhibition LXR, liver X receptor RXR retinoid X receptor SREBP, sterol regulatory element binding protein ChREBP, carbohydrate response element binding protein Mix, Max-like receptor PPAR-ot, peroxisome proliferator activated receptor alpha LXRE, liver X receptor response element SRE, sterol response element ChoRE, carbohydrate response element PPRE, peroxisome proliferator response element. (See color plate section, plate no. 6.)...

PPARs belong to a family of nuclear transcription factors that heterodimerize with retinoid X receptors (RXR) and function in a ligand-dependent manner [5]. They can activate transcription through binding peroxisome proliferator activated receptor response elements (direct repeat of AGGTCA spaced by one nucleotide). To date, three different PPAR isoforms a, 5/p, and y (and splice variants) have been identified that are encoded by separate genes. The tissue-specific expression pattern of these transcription factors is indicative of their function in those tissues [6]. 

The abbreviations used are HMG-CoA, 3-hydroxy-3-melhylglutaryl-CoA CAT, chloramphenicol acetyltransferase PPAR, peroxisome proliferator-activated receptor PPRE, peroxisome proliferator-responsive element NRRE, nuclear receptor responsive element RXR, retinoid X receptor hRXRa, human 9-cis-retinoic acid receptor a mPPARa, mouse peroxisome proliferator-activated receptor a COUP-TP, chicken ovalbumin upstream-promoter transcription factor, HNF-4, hepatocyte nuclear factor 4 EMSA, electrophoretic mobility shift analysis tk, thymidine kinase NEFA, nonesterified fatty acids... 

---