TRANSCRIPTIONAL REPRESSION BY RING FINGER PROTEIN TIF1-BETA THAT INTERACTS WITH THE KRAB REPRESSOR DOMAIN OF KOX1

Many of the vertebrate zinc finger factors of the Kruppel type (C2H2 z inc fingers) contain in their N-terminus a conserved sequence referred to as the KRAB (Kruppel-associated box) domain that, when tethered to DNA, efficiently represses transcription. Using the yeast two-hybrid system, we have isolated an 835 amino acid RING finger (C3HC4 zinc fin ger) protein, TIF1 beta (also named KAP-1), that specifically interact s with the KRAB domain of the human zinc finger factor KOX1/ZNF10. TIF 1 beta, TIF1 alpha, PML and efp belong to a characteristic subgroup of RING finger proteins that contain one or two other Cys/His-rich clust ers (B boxes) and a putative coiled-coil in addition to the classical C3HC4 RING finger motif (RBCC configuration), Like TIF1 alpha, TIF1 be ta also contains an additional Cys/His cluster (PHD finger) and a brom o-related domain. When tethered to DNA, TIF1 beta can repress transcri ption in transiently transfected mammalian cells both from promoter-pr oximal and remote (enhancer) positions, similarly to the KRAB domain i tself. We propose that TIF1 beta is a mediator of the transcriptional repression exerted by the KRAB domain.