MEMBERS OF THE CAUDAL FAMILY OF HOMEODOMAIN PROTEINS REPRESS TRANSCRIPTION FROM THE HUMAN APOLIPOPROTEIN-B PROMOTER IN INTESTINAL-CELLS

Apolipoprotein B (apoB) is the major protein component of low density lipoproteins, and plays a central role in cholesterol transport and me tabolism, The apoB gene is transcribed in the liver and in the intesti ne in humans. Although much is known about the DNA sequence elements a nd protein factors that are important for transcription of the human a polipoprotein B gene in the liver, less is known about the mechanisms that control transcription of this gene in the intestine, The sucrose isomaltase gene (SI), is expressed exclusively in the intestine, Two s equences from the promoter region of the SI gene, namely SIF-1 and SIF -3, are essential for promoter activity of the SI gene in intestinal c ells, Sequences displaying a high degree of similarity to those of SIF -1 and SIF-3 are present in the third intron of the apoB gene, Rather than stimulating apoB promoter activity, the BSIF-1 and BSIF-3 sequenc es repressed transcription in CaCo-2 cells, Gel retardation studies de monstrated that BSIF-1, like SIF-1, binds to proteins related to the c audal family of proteins such as mCdx-4 and mCdx-2. These proteins app ear to repress transcription from the apoB promoter by a mechanism tha t involves an interaction with members of the C/EBP family of proteins , that bind to a target sequence for the repressor in the segment from -139 to -111 of the apoB pro meter, On the other hand, BSIF-3, like S IF-S, binds to HNF-1 and also represses transcription from the apoB pr omoter.