Pioneer activity of an oncogenic fusion transcription factor at inaccessible chromatin

Recent advances in the characterization of pioneer factors have led to new questions about domain structures and chromatin recognition. Seemingly separate fields have integrated common scientific problems with the identification of fusion pioneer factor (PF) pairs in childhood cancers. Excitingly, this represents a convergence of fields within science, of pediatric oncology, genomics, epigenetics, and biophysics. With PF-pairs emerging as driver oncogenes in childhood rhabdomyosarcoma (RMS), our studies investigate these fusion genes as a gestalt phenomenon, where the whole might equal more than the sum of the parts. We developed a new method for ChIP-seq with per-cell normalization (pc-ChIP-seq) to simultaneously define genome size and PAX3-FOXO1 localization in RMS. We report novel pioneer function for the major driver oncogene in RMS, with nucleosome-motif targeting and kinetic displacement of nucleosomes in human cells.