FXRE can function as an LXRE in the promoter of human ileal bile acid‐binding protein (I‐BABP) gene

FEBS Letters

Demydchuk, Julia¹  Landrier, Jean-François¹  Grober, Jacques¹  Besnard, Philippe¹ 

[1] Physiologie de la Nutrition, Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l’Alimentation (ENSBANA), UMR 5170 CNRS/INRA/Université de Bourgogne, 1 esplanade Erasme, F-21000 Dijon, France

关键词: Ileal bile acid-binding protein;    Liver X-receptor;    Farnesoid X-receptor;    Cholesterol;    Bile acid;    Fatty acid-binding protein;    Small intestine;    Nuclear receptor;    BA;    bile acids;    CS;    cholesterol;    I-BABP;    ileal bile acid-binding protein;    FXR;    farnesoid X-receptor;    LXR;    liver X-receptor;    RXR;    retinoid X-receptor;    FXRE;    FXR-responsive element;    LXRE;    LXR-responsive element;    SRE;    sterol-responsive element;    I-BAT;    ileal bile acid transporter;    FAS;    fatty acid synthase;    PLTP;    phospholipid transfer protein;    SREBP;    sterol regulatory element-binding proteins;    CAT;    chloramphenicol acetyltransferase;   

DOI  :  10.1016/S0014-5793(03)01033-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown