The -700/-310 fragment of the apolipoprotein A-IV gene combined with the -890/-500 apolipoprotein C-III enhancer is sufficient to direct a pattern ofgene expression similar to that for the endogenous apolipoprotein A-IV gene

Spatial gene expression in the intestine is mediated by specific regulatory sequences. The three genes of the apoA-I/C-III/A-IV cluster are expressed in the intestine following cephalocaudal and crypt-to-villus axes. Previous studies have shown that the -780/-520 enhancer region of the apoC-III gene directs the expression of the apoA-I gene in both small intestinal villi a nd crypts, implying that other unidentified elements are necessary for a no rmal intestinal pattern of apoA-I gene expression. In this study, we have c haracterized transgenic mice expressing the chloramphenicol acetyltransfera se gene under the control of different regions of the apoC-III and apoA-IV promoters. We found that the -890/+24 apoC-III promoter directed the expres sion of the reporter gene in crypts and villi and did not follow a cephaloc audal gradient of expression. In contrast, the -700/+10 apoA-IV promoter li nked to the -500/-890 apoC-III enhancer directed the expression of the repo rter gene in enterocytes with a pattern of expression similar to that of th e endogenous apoA-IV gene. Furthermore, linkage of the -700/-310 apoA-IV di stal promoter region to the -890/+24 apoC-III promoter was sufficient to re store the appropriate pattern of intestinal expression of the reporter gene . These findings demonstrate that the -700/-310 distal region of the apoA-I V promoter contains regulatory elements that, in combination with proximal promoter elements and the -500/-890 enhancer, are necessary and sufficient to restrict apoC-III and apoA-IV gene expression to villus enterocytes of t he small intestine along the cephalocaudal axis.