Ubx orchestrates tissue identity through regional and bidirectional changes to chromatin accessibility

Hox proteins are homeodomain transcription factors that diversify serially homologous segments along the animal body axis, as revealed by the classic bithorax phenotype of Drosophila melanogaster where mutations in Ultrabithorax ( Ubx ) transform the third thoracic segment into the likeness of the second thoracic segment. To specify segment identity we show that Ubx both increases and decreases chromatin accessibility, coinciding with its role as both an activator and repressor of transcription. Surprisingly, whether Ubx functions as an activator or repressor differs depending on the proximal-distal position in the segment and the availability of Hox cofactors. Ubx-mediated changes to chromatin accessibility positively and negatively impact the binding of Scalloped (Sd), a transcription factor that is required for appendage development in both segments. These findings reveal how a single Hox protein can modify complex gene regulatory networks to transform the identity of an entire tissue.