Expression cloning of a zinc-finger cyclic AMP-response-element-binding protein

In response to specific extracellular signals, intracellular cyclic AMP levels increase, leading to a variety of responses including the alteration of transcription of many eukaryotic genes. This transcriptional effect is frequently mediated through the cyclic AMP-response element (CRE) motif T(T/G)ACGTCA. Using an expression screening approach we have cloned a yeast gene, MSN2, that encodes a 78 kDa protein that recognizes this consensus CRE motif. Phosphorylation of the MSN2 protein by the catalytic subunit of protein kinase A stimulates DNA binding in vitro. Two putative Cys2His2-type zinc fingers present in the C-terminal 79 amino acids of the MSN2 protein are sufficient to confer CRE-binding specificity. Therefore, MSN2 represents a novel CRE-binding protein distinct from the multiple previously characterized basic region-leucine zipper repeat CRE-binding proteins.