General Biology Seminar

A central question in biology is how enhancers become active as development proceeds. The Drosophila embryo is a good model system to study this question as the gene regulatory networks regulating early developmental events have been well characterized. Zelda (Zld) is a uniformly distributed transcription factor (TF) integral to these networks, acting prior to and in collaboration with the patterning TFs to regulate target enhancers. Here we test the hypothesis that Zld directs TF binding across the genome by displacing nucleosomes at enhancers. Our results indicate that early enhancers are characterized by an intrinsically high nucleosome barrier, which is overcome by Zld, and that without Zld, TF binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that enhancers are initially and globally defined by the binding of Zld, which locally decreases nucleosome occupancy, thereby assisting TFs in accessing their binding motifs and promoting enhancer activity.