The mouse genome contains two genes for Pygopus (Pygo), which was identified as a Wnt signalling component in Drosophila. All Pygo proteins contain a conserved plant homology domain (PHD) that allows them to bind di- and trimethylated lysine 4 on histone H3, but is histone binding required for Pygo to function in Wnt signalling? To investigate this question, Konrad Basler and colleagues have generated mice homozygous for a Pygo2 mutation that abolishes chromatin binding (p. ). Surprisingly, Pygo2-chromatin binding is not needed to maintain Pygo2 function during mouse development, and abrogation of the Pygo2-chromatin interaction has little effect on Wnt signalling-related transcription during tissue homeostasis. Compromised Pygo2-chromatin binding leads to male sterility, however, and the researchers report that PHD-dependent recruitment of Pygo to regulatory regions in the testes is important for the recruitment of the histone acetylase Gcn5 to chromatin. These results identify a testis-specific role for Pygo2 as a chromatin remodeller that is unrelated to its role as a modulator of Wnt signalling.
