C-terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate polycomb proteins

Polycomb (Pc) is part of a Pc group (PcG) protein complex that is involved in repression of gene activity during Drosophila and vertebrate development . To identify proteins that interact with vertebrate Pc homologs, we perfor med two-hybrid screens with Xenopus Pc (XPc) and human Pc 2 (HPC2). We find that the C-terminal binding protein (CtBP) interacts with XPc and HPC2, th at CtBP and HPC2 coimmunoprecipitate, and that CtBP and HPC2 partially colo calize in large PcG domains in interphase nuclei. CtBP is a protein with un known function that binds to a conserved 6-amino-acid motif in the C termin us of the adenovirus E1A protein. Also, the Drosophila CtBP homolog interac ts, through this conserved amino acid motif, with several segmentation prot eins that act as repressors. Similarly, we find that CtBP binds with HPC2 a nd XPc through the conserved 6-amino-acid motif. Importantly, CtBP does not interact with another vertebrate Pc homolog, M33, which lacks this amino a cid motif, indicating specificity among vertebrate Pc homologs. Finally, we show that CtBP is a transcriptional repressor. The results are discussed i n terms of a model that brings together PcG-mediated repression and repress ion systems that require corepressors such as CtBP.