Negative and positive promoter elements contribute to tissue specificity of apolipoprotein B expression.

Apolipoprotein B (ApoB) is a major constituent of the plasma lipoproteins. In adult mammals it is synthesized in two different tissues, liver and intestine. We have examined the promoter elements involved in determining the cell specificity of apoB expression, using a chloramphenicol acetyltransferase assay and the cell lines HepG2, CaCo-2 and HeLa. The human apoB promoter contains: (i) a strong, cell-specific, positive element which can act on a heterologous promoter. This element is located between pos -111 and -33 and is built up by three subdomains, two positive and one negative; (ii) a large, negative element between pos -639 and -129, which reduces promoter activity in apoB expressing cells (HepG2 and CaCo-2) and block activation of the promoter by the SV40 enhancer in non-expressing cells (HeLa); (iii) a positive element in the noncoding part of exon 1 which retains its activity if placed upstream from the other regulatory elements and stimulates transcription from the simian virus 40 promoter in all three cell lines. The same sequence elements appear to be important for expression in cells of hepatic (HepG2) and intestinal (CaCo-2) origin.