HUMAN APOLIPOPROTEIN A-IV GENE-EXPRESSION IS MODULATED BY MEMBERS OF THE NUCLEAR HORMONE-RECEPTOR SUPERFAMILY

Human apolipoprotein A-IV (apo A-IV) is essentially synthesized in int estine and to a lower extent in liver. The presence of detectable amou nts of apo A-IV messenger in HepG2 and Caco-2 cells enables us to stud y the transcription regulation of the gene in these cells. A main hype rsensitive site to DNase I is detected in the DNA of HepG2 nuclei, in a region situated about 3400 base pairs upstream from the cap site. Tr ansient expression experiments in HepG2, Caco-2 and HeLa cells indicat e that HNF-4 activates the transcription of a reporter gene through th e -3500/+67 sequence of the apo A-IV gene. This activation is represse d by another transcription factor, Ear3/COUP-TF. On the contrary, HNF- 1, whose expression is controlled by HNF-4, is not involved in the reg ulation of the reporter gene transcription through the -6700/+67 genom e sequence. These results indicate that the apo A-IV gene expression i s modulated by orphan ligand members of the superfamily of nuclear hor mone receptors.