GLI proteins are bifunctional DNA-binding proteins that recognize consensus GLI sites 5'-GACCACCC-3' in the promoters of target genes (Kinzler and Vogelstein, 1990). Pathway induction upon ligand-binding diverts the GLI proteins from the processing/degradation pathway that generates the truncated repressor form and promotes the formation of the full-length transcriptional activator (reviewed in Hui and Angers, 2011; Briscoe and Therond, 2013). GLI-dependent target genes have been identified by a number of ChIP based screens, and well-established, direct targets include a number of Hh pathway members including PTCH1, PTCH2, GLI1, HHIP and BOC (Lee et al, 2010; Vokes et al, 2007; Vokes et al, 2008; Agren et al, 2004; Bai et al, 2004; Bai et al, 2002; Dai et al, 1999). Full-length GLI proteins nucleate the assembly of a transcriptional activation complex at target gene promoters, but the details of interacting partners are not well known. The C-terminus of GLI3 has been shown to interact with a number of transcriptional activators including the histone acetyltransferase CBP, the Mediator component Med12 and the TATA-box recognition protein TAF31, but the detail of how and when these binding partners interact is not known (Dai et al, 1999; Zhou et al, 2006; Yoon et al, 1998; reviewed in Hui and Angers, 2011). Each of the GLI proteins has been shown to bind to CDC 73, a component of the PAF complex that has roles in RNA polymerase II-mediated transcription (Mosimann et al, 2009; reviewed in Tomson and Arndt, 2013).