Bile acid response element

Expression of IBABP and ASBT is regulated by the famesoid X receptor (FXR), a nuclear orphan receptor (246, 247). A specific binding site for F3 was found on the promotor region of the IBABP gene, named bile acid response element (BARE) (248). The response was greatest in the presence of chenodeoxy-cholic acid (CDCA), whereas cholic acid was much less effective and the secondary bile acids deoxycholic and lithocholic acid had variable responses. 

Grober, J., Zaghini, I., Fujii, H., Jones, S. A., Kliewer, S. A., Willson, T. M., Ono, T., and Besnard, P. (1999) Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the famesoid X receptor/9-cis-retinoic acid receptor heterodimer../. Biol. Chem. 274, 29749-29754. 

Chiang JYL, Stroup D (1994) Identification and characterization of a putative bile acid-responsive element in cholesterol 7a-hydroxylase gene promoter. J Biol Chem 269 17502-17507... 

Hormones and vitamins also play a role in regulation of ASBT. Both glucocorticoid receptor ligands and co-expression of the glucocorticoid receptor gene increased activity of ASBT, while there is also evidence that dihydroxy vitamin D binds directly to the vitamin D response element and increases expression of ASBT, leading to increased transport of bile acids into the enterocyte. ... 

VDR has also been demonstrated to be an intestinal receptor for the toxic secondary bile acid LCA [122], Activation of VDR by vitamin D or LCA induces expression of CYP3A4 that can detoxify LCA via phase I hydroxylation [122], Low expression of VDR in hepatocytes [123] and the coexpression of VDR and CYP3 A4 in enterocytes indicate that dietary vitamin D may modulate first-pass drug metabolism in the intestine. The murine multispecific anion transporter Mrp3, which is also expressed in intestine, harbors a VDR response element in its promoter region and is transactivated upon calcitriol and LCA treatment [124], VDR-stimulated Mrp3 expression could thus further contribute to intestinal first-pass drug metabolism. 

Fig. 7. Induction of Cyp7al gene expression by oxysterol-activated LXRa RXRa. Both the bile acid and cholesterol biosynthetic pathways generate oxysterols. The binding site of LXRaiRXRa in the Cyp7al gene promoter is a DR-4 element (a direct repeat of the hexanucleotide hormone response element separated by 4 nt).

Agellon, L.B., Cheema, S.K. 1997. The 3 -untranslated region of the mouse cholesterol 7a-hydroxylase contains elements responsive to posttranscriptional regulation by bile acids. Biochem. J. 328 393-399. 

Figure 8.1. A model of the transcriptional regulation of CYP3A expression by PXR. The PXR binds as a heterodimer with RXR to response elements in the promoter of CYP3A and other target genes. Binding of ligand to the PXR results in increased CYP3A enzyme activity, which in turn increases the hydroxylation of substrates such as steroids, bile acids, and drugs,...

---