Pioneer factor GAF cooperates with PBAP and NURF to regulate transcription

Transcriptionally silent genes must be activated throughout development. This requires nucleosomes be removed from promoters and enhancers to allow transcription factor binding (TFs) and recruitment of coactivators and RNA Polymerase II (Pol II). Specialized pioneer TFs bind nucleosome-wrapped DNA to perform this chromatin opening by mechanisms that remain incompletely understood. Here, we show that GAGA-factor (GAF), a Drosophila pioneer factor, interacts with both SWI/SNF and ISWI family chromatin remodelers to allow recruitment of Pol II and entry to a promoter-proximal paused state, and also to promote Pol II9s transition to productive elongation. We found that GAF functions with PBAP (SWI/SNF) to open chromatin and allow Pol II to be recruited. Importantly this activity is not dependent on NURF as previously proposed; however, GAF also functions with NURF downstream of this process to ensure efficient Pol II pause release and transition to productive elongation apparently through its role in precisely positioning the +1 nucleosome. These results demonstrate how a single sequence-specific pioneer TF can synergize with remodelers to activate sets of genes. Furthermore, this behavior of remodelers is consistent with findings in yeast and mice, and likely represents general, conserved mechanisms found throughout Eukarya.