The KRAB repression domain is one of the most widely distributed trans
criptional effector domains yet identified, but its mechanism of repre
ssion is unknown. We have cloned a corepressor, KAP-1, which associate
s with the KRAB domain but not with KRAB mutants that have lost repres
sion activity. KAP-1 can enhance KRAB-mediated repression and is a rep
ressor when directly tethered to DNA. KAP-1 contains a RING finger, B
boxes, and a PHD finger; the RING-B1-B2 structure is required for KRAB
binding and corepression. We propose that KAP-1 may be a universal co
repressor for the large family of KRAB domain-containing transcription
factors.