PROXIMAL REGULATORY DOMAINS OF RAT ATRIAL-NATRIURETIC-FACTOR GENE

Background. At least three cis-acting regulatory elements are required for expression of the rat atrial natriuretic factor (ANF) gene. One distal cis-acting regulatory element lies more than 640 base pairs from the transcription initiation site. Methods and Results. In this report, we identify two other proximal regulatory elements that lie within 609 base pairs of the transcription initiation site. One proximal regulatory element contains an activator protein-1 (AP-1)-like binding site and is recognized by the AP-1 protein, the c-fos/c-jun proto-oncogene heterodimer in vitro. The second regulatory element contains a cyclic AMP-responsive element (CRE)-like recognition site. Conclusions. In vitro binding of the c-fos/c-jun heterodimer to ANF gene sequences suggests that the heterodimer may play a role in the regulation of gene transcription in vivo. This observation may also explain the correlation between c-fos/c-jun expression and ventricular ANF gene expression found in hypertrophic states. Nuclear extracts from normal cardiocytes contain proteins that bind these regulatory elements but do not appear to bind at the AP-1 site, suggesting that the levels of fos/jun heterodimer in nonhypertrophied cardiocytes are quite low.