INTERACTION OF PC4 WITH MELTED DNA INHIBITS TRANSCRIPTION

PC4 is a nuclear DNA-binding protein that stimulates activator-depende nt class II gene transcription in vitro. Recent biochemical and X-ray analyses have revealed a unique structure within the C-terminal domain of PC4 that binds tightly to unpaired double-stranded (ds)DNA. The ce llular function of this evolutionarily conserved dimeric DNA-binding f old is unknown. Here we demonstrate that PC4 represses transcription t hrough this moth. Interaction with melted promoters is not required fo r activator-dependent transcription in vitro. The inhibitory activity is attenuated on bona fide promoters by (i) transcription factor TFIIH and (ii) phosphorylation of PC4. PC4 remains a potent inhibitor of tr anscription in regions containing unpaired ds DNA, in single-stranded DNA that can fold into two antiparallel strands, and on DNA ends. Our observations are consistent with a novel inhibitory function of PC4.