Biochem Biophys Res Commun. 1996 Aug 14;225(2):585-92.  

The opposing effects of retinoic acid and phorbol esters converge to a common
response element in the promoter of the rat cholesterol 7 alpha-hydroxylase gene
(CYP7A).

Crestani M, Sadeghpour A, Stroup D, Galli G, Chiang JY.

Department of Biochemistry and Molecular Pathology, Northeastern Ohio
Universities College of Medicine, Rootstown 44272-0095, USA.

The activity of the rat CYP7A/luciferase reporter gene was increased five-fold
by all-trans retinoic acid (atRA) or 9-cis retinoic acid (9cRA) in transient
transfection assay in HepG2 cells. Cotransfection with retinoid X receptor (RXR)
stimulated the promoter activity in the absence of ligand, however, addition of
atRA inhibited the transcriptional activity. Cotransfection with retinoic acid
receptor (RAR) did not have much effect on CYP7A promoter activity. The CYP7A
promoter, when linked upstream to the SV40/ luciferase reporter gene, strongly
repressed the phorbol 12-myristate 13-acetate (PMA)-stimulated SV40/ luciferase
reporter gene activity. The regions conferring the effects of RA and PMA were
mapped to nt-176/ -117 and nt-148/-129, respectively. Several direct repeats of
hormone response element (AGTTCA) in this region are required for RA response.
AP-1 like sequences are located within the region responding to both RA and PMA.
Site-directed mutagenesis of the AP-1 site abolished the effects of both RA and
phorbol esters. Retinoic acid effect was antagonized by PMA. Moreover,
cotransfection of Fos and Jun expression vectors blunted the stimulatory effect
of retinoic acid on the CYP7A/luciferase gene activity. Therefore, effects of
two different signal transduction pathways converge to a common response
element. This regulatory cross-talk may be involved in bile acid repression and
regulates CYP7 gene transcription in the liver.

PMID: 8753804 [PubMed - indexed for MEDLINE]