The mechanisms by which a human apolipoprotein B gene enhancer and reducer interact with the promoter are different in cultured cells of hepatic and intestinal origin.

In the preceding paper (Paulweber, B., Onasch, M. A., Nagy, B. P., and Levy-Wilson, B. (1991) J. Biol. Chem. 266, 24149-24160) we demonstrated that the segment of the apolipoprotein B promoter extending from -260 to -85 is functionally different in hepatic (HepG2) and intestinal (CaCo-2) cells. These functional differences could be explained at least in part by differences in binding of three nuclear proteins to the region from -111 to -88. In this article we present further evidence suggesting that the mechanisms involved in transcriptional control of the apolipoprotein B gene in HepG2 and CaCo-2 cells are different, by demonstrating that an enhancer and a reducer can alter the activity of various apolipoprotein B promoter segments in widely differing ways in these two cell lines. Furthermore, we have localized a 329-base pair segment that is found within a negative regulatory region in the 5' distal portion of the gene. It displays a strong reducer effect upon promoter sequences that exhibit maximal transcriptional activity in CaCo-2 cells, but not in HepG2 cells.