The FBP Interacting Repressor Targets TFIIH to Inhibit Activated Transcription

Abstract

FUSE-binding protein (FBP) binds the single-stranded far upstream element of active c- myc genes, possesses potent transcription activation and repression domains, and is necessary for c- myc expression. A novel 60 kDa protein, the FBP interacting repressor (FIR), blocked activator-dependent, but not basal, transcription through TFIIH. Recruited through FBP's nucleic acid–binding domain, FIR formed a ternary complex with FBP and FUSE. FIR repressed a c- myc reporter via the FUSE. The amino terminus of FIR contained an activator-selective repression domain capable of acting in cis or even in trans in vivo and in vitro. The repression domain of FIR targeted only TFIIH's p89/XPB helicase, required at several stages in transcription, but not factors required for promoter selection. Thus, FIR locks TFIIH in an activation-resistant configuration that still supports basal transcription.