Cell fate commitment relies on both activation of appropriate genes and suppression of inappropriate ones. The Polycomb group (PcG) proteins are crucial epigenetic silencers of developmental genes, but the manner by which they control fate in vivo, and the relative roles of different PcG proteins in silencing, have remained unclear. Now, Justin Kumar and colleagues examine the role of PcG proteins in Drosophila eye development. Knockdown of Polycomb, a member of the PRC1 complex, in the developing eye disc leads to a dramatic eye-to-wing transformation. These transformations are accompanied by adoption of wing-specific gene expression patterns, and de-repression of the Hox gene Antp in a manner dependent on the transcription factor Tsh. Interestingly, knockdown of another PcG complex, PhoRC, results in eye-to-wing transformations only if retinal determination Pax6 genes are simultaneously knocked down; downstream targets of Pax6 do not recapitulate this effect. Indeed, the authors find that different PcG proteins have distinct functions in maintaining cellular memory, and that they act at distinct developmental time points to carry out their repressive functions. This work therefore provides molecular insight into how distinct epigenetic silencers, together with tissue-specific gene regulatory networks, work to maintain cell fate during development.
