The 3'-flanking region shared by the human apolipoprotein AI and CIII gene regulates gene expression in cooperation...

The genes of the apolipoproteins AI and CIII are localized in opposite orientation on chromosome 11 in close vicinity, separated from each other by a non-coding intergenic region of 2.1 kb. The interdependence of their expression has been studied in cotransfection experiments in Hep G2 cells. An expression vector harboring the intergenic region with CAT as reporter gene and likewise pUC 19 derivatives with the putative cis-elements were constructed. Inhibition of gene expression by 5'-flanking elements of the apo AI and CIII gene was observed. Four proteins have been identified in nuclear extracts of Hep G2 cells that bind to several sequences of the intergenic domain but not to the 5'-flanking regions of apo AI or CIII gene. These proteins might be responsible for the silencer effect. The pathway of the regulation of apo CIII and AI expression derived from the experiments described here is supported by mutations in the intergenic region, leading to the phenotype of hypertriglyceridemia, and the stimulatory effect of cholesterol on apo AI transcription in Hep G2 cells.