YEAST SUB1 IS A SUPPRESSOR OF TFIIB MUTATIONS AND HAS HOMOLOGY TO THEHUMAN COACTIVATOR PC4

Activation of transcription in eukaryotes depends upon the interplay b etween transcriptional activators and general transcription factors. W hile direct contacts between activators and general factors have been demonstrated in vitro, an additional class of proteins, termed co-acti vators, is also required for transcriptional activation. Here we descr ibe a yeast protein, SUB1, that was isolated as a suppressor of the co ld-sensitive TFIIB R78H mutant. The N-terminal third of SUB1 is highly similar to the mammalian co-activator PC4. We show that increased exp ression of SUB1 suppresses two alleles of TFIIB (E62G, R78H) specifica lly and that the deletion of SUB1 is lethal in combination with these same two alleles. We show that SUB1 binds to TFIIB in vitro and that i t specifically inhibits the formation of TBP-TFIIB-promoter complexes. Furthermore we show that increasing the copy number of SUB1 stimulate s transcriptional activation in vivo. Based on our results and recent observations of others, we propose that SUB1 plays a role in the relea se of TFIIB from the transcription complex during transcription initia tion.