Pioneer and nonpioneer cooperation drives lineage specific chromatin opening

Pioneer transcription factors are coined as having the unique property of "opening closed chromatinsites" for implementation of cell fates. We previously showed that the pioneer Pax7specifies melanotrope cells through deployment of an enhancer repertoire: this allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigated the relation between these two factors in the pioneer mechanism. Cell-specific gene expression and chromatinlandscapes were defined by scRNAseq and chromatinaccessibility profiling. We found that in vivo deployment of the melanotrope enhancer repertoireand chromatinopening requires both Pax7and Tpit. In cells, binding of heterochromatintargets by Pax7is independent of Tpit but Pax7-dependent chromatinopening requires Tpit. The present work shows that pioneer core properties are limited to the ability to recognize heterochromatintargets and facilitate nonpioneer binding. Chromatinopening per se may be provided through cooperation with nonpioneer factors.