HNF-4 increases activity of the rat Apo A1 gene

Open Access
Publisher Website
Google Scholar
Abstract
Apollpoprotein A1 (Apo A1) is the major protein component of high density Ilpoprotein (HDL) particles. HDL particles mediate the removal of cholesterol from extra-hepatic tissues via a process known as reverse cholesterol transport. Augmented production of Apo A1 will likely be beneficial to those who suffer from the consequences of hypercholesterolemla. One approach to increase expression of the protein is to identify nuclear factor(s) that enhance Apo A1 promoter activity. Therefore, we have used transient transfectlon to study a limited portion (∼474 to − 7) of the gene and showed that a cls-regulatory element, site C had a permissive effect on the ability of an adjacent site B to increase promoter activity by 30-fold. The Importance of element C prompted us to identify the factors) that interact with this site. Results showed that HNF-4, a new member of the thyroid/steroid hormone receptor superfamlly interacts with site C to enhance activity of the promoter. Based on this observation and that of the known Inhibitory effects of ARP-1 on site C, we postulate a model which may account for the tissue-specific expression of the rat Apo A1 gene.