Pax7 remodels the chromatin landscape in skeletal muscle stem cells

The mechanisms by which Pax7 promotes skeletal muscle stem (satellite) cell identity are not yet understood. We have taken advantage of pluripotent stem cells wherein the induced expression of Pax7 robustly initiates the muscle program and enables the generation of muscle precursors that repopulate the satellite cell compartment upon transplantation. Pax7 binding was excluded from H3K27 tri-methylated regions, suggesting that recruitment of this factor is circumscribed by chromatin state. Further, Pax7 binding provoked localized chromatin remodeling, including the acquisition of enhancer-associated histone marks and induction of chromatin accessibility. Conversely, removal of Pax7 led to rapid reversal of these features on a subset of enhancers. Another cohort of Pax7 binding sites exhibited a durably accessible and remodeled chromatin state after Pax7 removal, and persistent enhancer accessibility was associated with subsequent binding by muscle regulatory factors. Our studies provide new insights into Pax7 and the epigenetic landscape of skeletal muscle stem cells. Examining the role of Pax7 in myogenesis and the chromatin context of Pax7-bound regions. (1) RNA-seq in the presence and absence of doxycyline (dox, inducing Pax7-expression) through the inducible iPax7-cell system (2) ChIP-seq of Pax7, H3K27Ac, H3K4me1, H3K4me3, and H3K27me3 in the presence and absence of dox in iPax7 myogenic progenitors (3) ATAC-seq of satellite cells, myogenic progenitors, myoblasts