Regulation of the ANF and BNP promoters by GATA factors: Lessons learned for cardiac transcription

The identification and molecular cloning of the cardiac transcription facto rs GATA-4, -5, and -6 has greatly contributed to our understanding of how t issue-specific transcription is achieved during cardiac growth and developm ent. Through analysis of their interacting partners, it has also become app arent that a major mechanism underlying spatial and temporal specificity wi thin the heart as well as in the response to cardiogenic regulators is the combinatorial interaction between cardiac-restricted and inducible transcri ption factors. The cardiac GATA factors appear to be fundamental contributo rs to these regulatory networks. Two of the first targets identified for th e cardiac GATA factors were the natriuretic peptide genes encoding atrial n atriuretic factor (ANF) and B-type natriuretic peptide (BNP), the major hea rt secretory products that are also accepted clinical markers of the diseas ed heart. Studies using the ANF and BNP promoters as models of cardiac-spec ific transcription have unraveled the pivotal role that GATA proteins play in cardiac gene expression. We review the current knowledge on the modulati on of the natriuretic peptide promoters by GATA factors, including examples of combinatorial interactions between GATA proteins and diverse transcript ion factors.