Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation

  1. Christine Rushlow1
  1. 1Department of Biology, New York University, New York, New York 10003-6688, USA;
  2. 2Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
  3. 3Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, Kansas 66160, USA
  1. Corresponding authors: car2{at}nyu.edu, jbz{at}stowers.org
  1. 4 These authors contributed equally to this work.

Abstract

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.

Footnotes

  • [Supplemental material is available for this article.]

  • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.192542.115.

  • Freely available online through the Genome Research Open Access option.

  • Received March 27, 2015.
  • Accepted August 20, 2015.

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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