Members of the Caudal Family of Homeodomain Proteins Repress Transcription from the Human Apolipoprotein B Promoter in Intestinal Cells

doi:10.1074/jbc.271.2.707

Members of the Caudal Family of Homeodomain Proteins Repress Transcription from the Human Apolipoprotein B Promoter in Intestinal Cells (*)

From the (1)Palo Alto Medical Foundation Research Institute, Palo Alto, California 94301
(2)Gladstone Institute for Cardiovascular Disease, and
(3)First Department of Internal Medicine, Landeskrankenantalten, Salzburg, Austria

^§§ To whom correspondence should be addressed:
Palo Alto Medical Foundation, Research Institute, 860 Bryant St., Palo Alto, CA 94301.
Tel.: 415-326-8120; Fax: 415-329-9114.

↵^§ Present address: Dept. of Pediatrics, Stanford University School of Medicine, Stanford, CA 94303.
↵^¶ Present address: C.V. Therapeutics, Palo Alto, CA 94304.
↵** Present address: Dept. of Pathology, Stanford University School of Medicine, Stanford, CA 94303.

Abstract

Apolipoprotein B (apoB) is the major protein component of low density lipoproteins, and plays a central role in cholesterol transport and metabolism. The apoB gene is transcribed in the liver and in the intestine in humans. Although much is known about the DNA sequence elements and protein factors that are important for transcription of the human apolipoprotein 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 sequences 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 cells. 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 sequences repressed transcription in CaCo-2 cells. Gel retardation studies demonstrated that BSIF-1, like SIF-1, binds to proteins related to the caudal family of proteins such as mCdx-4 and mCdx-2. These proteins appear to repress transcription from the apoB promoter by a mechanism that 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 promoter. On the other hand, BSIF-3, like SIF-3, binds to HNF-1 and also represses transcription from the apoB promoter.

Footnotes

↵* Part of this research was supported by a National Institutes of Health Research Grant HL41633 (to B. L. W.). The bulk of this research was supported by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California, Grant 4RT-0308A. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

HNF

hepatocyte nuclear factor

apoB

apolipoprotein B

SI

sucrose isomaltase

CaCo

colon carcinoma

CAT

chloramphenicol acetyltransferase

TBP

TATA-binding protein

bp

base pair(s).
↵²B. Levy-Wilson, unpublished observation.
- Received August 29, 1995.
- Revision received October 31, 1995.