FXRE can function as an LXRE in the promoter of human ileal bile acid-binding protein (I-BABP) gene.
Ileal bile acid-binding protein (I-BABP) is a 14 kDa cytosolic protein which binds bile acids with a high affinity. It is thought to be implicated in the enterohepatic circulation of bile acids and, hence, in cholesterol homeostasis. Using a combination of in vivo and in vitro experiments, we have recently shown that I-BABP gene expression can be indirectly up-regulated by cholesterol through the activation of sterol-responsive element-binding protein 1c (SREBP1c) by liver X-receptor (LXR). We report here that I-BABP can be also a direct target for LXR. I-BABP regulation by LXR is maintained when the SREBP binding site is deleted in the I-BABP promoter and occurs, in the absence of conventional LXRE sequences, through an IR1 sequence previously identified as a farnesoid X-receptor-responsive element (FXRE). Electrophoretic mobility shift assays demonstrated that the LXR/RXR heterodimer specifically recognizes the FXRE. Collectively, these data strongly suggest that LXR can regulate the I-BABP gene by both direct and indirect mechanisms.
Physiologie de la Nutrition, Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation, Université de Bourgogne, 1 esplanade Erasme, F-21000, Dijon, France.
Jean-François
JF
Landrier
Jacques
J
Grober
Julia
J
Demydchuk
Philippe
P
Besnard
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000378:metabolism; D001665:Binding Sites; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D007082:Ileum / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D013261:Sterols / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D001565:Benzoates; D001596:Benzylamines; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D015500:Chloramphenicol O-Acetyltransferase; D004268:DNA-Binding Proteins; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013261:Sterols; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C473027:GW 3965; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)