RT Journal A1 Sun, Yujia A1 Nien, Chung-Yi A1 Chen, Kai A1 Liu, Hsiao-Yun A1 Johnston, Jeff A1 Zeitlinger, Julia A1 Rushlow, Christine T1 Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation JF Genome Research JO Genome Research YR 2015 FD November 01 VO 25 IS 11 SP 1703 OP 1714 DO 10.1101/gr.192542.115 UL http://genome.cshlp.org/content/25/11/1703.abstract AB The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner.