In multicellular eukaryotes, Polycomb repression heritably silences gene expression programs not needed or detrimental for a given developmental stage or tissue (Schuettengruber et al., 2017). During cell fate reprogramming, Polycomb silencing can be overcome by the combined activity of multiple Trithorax group (TrxG) proteins (Wu et al., 2012; Liang et al., 2015; Schuettengruber et al., 2017). TrxG proteins are genetically defined as suppressors of homeotic defects caused by loss of Polycomb function and have diverse enzymatic activities (Schuettengruber et al., 2017). We used a genetic enhancer screen to identify candidate TrxG proteins and uncovered TrxG activity for components of the SWR1 chromatin remodeling complex, which deposits the histone variant H2A.Z (Deal et al., 2007; March-Diaz et al., 2008). Read more