EXPRESSION CLONING OF A ZINC-FINGER CYCLIC AMP-RESPONSE-ELEMENT-BINDING PROTEIN

In response to specific extracellular signals, intracellular cyclic AM P levels increase, leading to a variety of responses including the alt eration of transcription of many eukaryotic genes. This transcriptiona l effect is frequently mediated through the cyclic AMP-response elemen t (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 rec ognizes this proteins. consensus CRE motif. Phosphorylation of the MSN 2 protein by the catalytic subunit of protein kinase A stimulates DNA binding in vitro. Two putative Cys(2)His(2)-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 CR E-binding protein distinct from the multiple previously characterized basic region-leucine zipper repeat CRE-binding proteins.