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 intestine and to a lower extent in liver. The presence of detectable amounts of apo A-IV messenger in HepG2 and Caco-2 cells enables us to study the transcription regulation of the gene in these cells. A main hypersensitive 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. Transient expression experiments in HepG2, Caco-2 and HeLa cells indicate that HNF-4 activates the transcription of a reporter gene through the -3500/+67 sequence of the apo A-IV gene. This activation is repressed by another transcription factor, Ear3/COUP-TF. On the contrary, HNF-1, whose expression is controlled by HNF-4, is not involved in the regulation of the reporter gene transcription through the -6700/+67 genome sequence. These results indicate that the apo A-IV gene expression is modulated by orphan ligand members of the superfamily of nuclear hormone receptors.