THE UPSTREAM ACTIVATOR CTF NF1 AND RNA-POLYMERASE-II SHARE A COMMON ELEMENT INVOLVED IN TRANSCRIPTIONAL ACTIVATION/

The carboxy-terminal domain (CTD) of the largest subunit of RNA polyme rase II consists of tandem repeats of a heptapeptide with the consensu s YSPTSPS. It has been shown that the heptapeptide repeat interacts di rectly with the general transcription factor TFIID. We report here tha t the CTD activates transcription when fused to the DNA-binding domain of GAL4. More importantly, we find that the proline-rich transcriptio nal activation domain of the CCAAT-box-binding factor CTF/NF1 contains a sequence with striking similarity to the heptapeptide repeats of th e CTD. We show that this CTD-like motif is essential for the transcrip tional activator function of the proline-rich domain of CTF/NF1. Delet ion of and point mutations in this CTD-like motif abolish the transcri ptional activator function of the proline-rich domain, while natural C TD repeats from RNA polymerase II are fully functional in place of the CTD-like motif. We further show that the proline-rich activation doma in of CTF/NF1 interacts directly with the TATA-box-binding protein (TB P), and that a mutation in the CTD-like motif that abolishes transcrip tional activation reduces the affinity of the proline-rich domain for TBP. These results demonstrate that a class of proline-rich activator proteins and RNA polymerase II possess a common structural and functio nal component which can interact with the same target in the general t ranscription machinery. We discuss the implications of these results f or the mechanisms of transcriptional activation in eucaryotes.