Polycomb group (PcG) genes encode transcriptional repressors that regulate gene expression during development. Most PcG genes encode subunits of chromatin-modifying complexes, but exactly how PcG proteins repress transcription is unclear. Now, Judith Kassis and colleagues report that Wapl, a cohesin-associated protein involved in cohesin removal from chromosomes, promotes PcG silencing in Drosophila (p. ). To identify genes involved in PcG silencing, the researchers conduct a screen for suppressors of silencing mediated by an engrailed PcG response element. They identify one of the suppressors obtained from this screen as waplAG, a dominant wapl mutation that produces a truncated Wapl protein. The researchers show that waplAG hemizygotes die as pharate adults (insects prior to emergence from pupae) but have an extra-sex-comb phenotype similar to that produced by mutations in PcG genes. Finally, the researchers show that Wapl-AG increases the stability of cohesin binding to polytene chromosomes. Together, these results suggest that increasing cohesin stability can interfere with PcG silencing, and that cohesin thus directly inhibits PcG function.
