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

FEBS Lett. 2003 Oct 23;553(3):299-303. doi: 10.1016/s0014-5793(03)01033-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Benzylamines / pharmacology
  • Bile Acids and Salts / metabolism
  • Binding Sites
  • Caco-2 Cells
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Chloramphenicol O-Acetyltransferase / analysis
  • Chloramphenicol O-Acetyltransferase / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Gene Expression Regulation
  • Humans
  • Hydroxysteroid Dehydrogenases*
  • Ileum / metabolism*
  • Male
  • Membrane Glycoproteins*
  • Mice
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / physiology
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Response Elements / physiology*
  • Sterols / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcriptional Activation / physiology

Substances

  • Benzoates
  • Benzylamines
  • Bile Acids and Salts
  • Carrier Proteins
  • DNA-Binding Proteins
  • GW 3965
  • Membrane Glycoproteins
  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Sterols
  • Transcription Factors
  • bile acid binding proteins
  • farnesoid X-activated receptor
  • Hydroxysteroid Dehydrogenases
  • AKR1C2 protein, human
  • Chloramphenicol O-Acetyltransferase