CCR4 IS A GLUCOSE-REGULATED TRANSCRIPTION FACTOR WHOSE LEUCINE-RICH REPEAT BINDS SEVERAL PROTEINS IMPORTANT FOR PLACING CCR4 IN ITS PROPER PROMOTER CONTEXT

The yeast CCR4 protein is required for the expression of a number of g enes involved in nonfermentative growth, including glucose-repressible ADH2, and is the only known suppressor of mutations in the SPT6 and S PT10 genes, two genes which are believed to be involved in chromatin m aintenance. We show here that although CCR4 did not bind DNA under the conditions tested, it was able to activate transcription when fused t o a heterologous DNA-binding domain. The transcriptional activation ab ility of CCR4, in contrast to that of many other activators, was gluco se regulated. Two activation domains one of which was glucose responsi ve and encompassed a glutamine-proline-rich region similar to that fou nd in other eukaryotic transcriptional factors were identified. The tw o transactivation regions, when separated from the leucine-rich repeat and the C terminus of CCR4, were unable to complement a defective ccr 4 allele, suggesting that the leucine-rich repeat and the C terminus m ake contacts that link the activation regions to the proper gene conte xt. Native immunoprecipitation of CCR4 revealed that CCR4 was complexe d with at least four other proteins. The leucine-rich repeat of CCR4 w as both necessary and sufficient for interaction with at least two of these factors. We propose that the leucine-rich repeat links CCR4 thro ugh its associated factors to its promoter context at ADH2 and other l oci where it is required for proper transcriptional regulation.