Illegitimate expression of apolipoprotein A-II in Caco-2 cells is due to chromatin organization

Transcriptional activity of the human apolipoprotein (apo) A-II promoter ha s been reported in transiently transfected Caco-2 cells, but not in the int estine in vivo. In the present study we established that the transcription of a stably transfected reporter gene under the control of the -911/+29 hum an apo A-II, decreases with the onset of the differentiation process. This decrease paralleled that of the expression of the endogenous apo A-II gene. The decrease in apo A-II expression is also followed by a marked increase in the expression of the intestine-specific apo A-TV gene, analyzed here as a marker of enterocytic differentiation. Using clonal glucose metabolic va riants of Caco-2 cells we have also observed that the lowest levels of apo A-Ill mRNA are associated with the lowest rates of glucose consumption. The illegitimate apo A-II transcriptional activity observed in Caco-2 cells is linked to the presence of DNase-I hypersensitive sites within the enhancer . This reflects a chromatin organization which allows, in Caco-2 cells as i n the liver, the communication between the apo A-II enhancer and the proxim al promoter, unlike what is observed in intestinal epithelial cells. (C) 19 99 Academic Press.