Pou5f3, SoxB1, and Nanog remodel chromatin on high nucleosome affinity regions at zygotic genome activation
- 1Department of Developmental Biology, Institute of Biology I, Faculty of Biology, Albert Ludwigs University of Freiburg, 79104, Freiburg, Germany;
- 2Department of Biological Sciences, East Tennessee State University, Johnson City, Tennessee 37614-1710, USA;
- 3Zoological Institute, Basel University, Basel, CH-4051 Switzerland;
- 4Department of Computer Science, Albert Ludwigs University of Freiburg, 79110, Freiburg, Germany;
- 5Center for Biological Systems Analysis (ZBSA), University of Freiburg, 79104, Freiburg, Germany;
- 6Signalling Research centers BIOSS and CIBSS, 79104, Freiburg, Germany;
- 7Institute of Developmental Biology RAS, 119991 Moscow, Russia
Abstract
The zebrafish embryo is transcriptionally mostly quiescent during the first 10 cell cycles, until the main wave of zygotic genome activation (ZGA) occurs, accompanied by fast chromatin remodeling. At ZGA, homologs of the mammalian stem cell transcription factors (TFs) Pou5f3, Nanog, and Sox19b bind to thousands of developmental enhancers to initiate transcription. So far, how these TFs influence chromatin dynamics at ZGA has remained unresolved. To address this question, we analyzed nucleosome positions in wild-type and maternal-zygotic (MZ) mutants for pou5f3 and nanog by MNase-seq. We show that Nanog, Sox19b, and Pou5f3 bind to the high nucleosome affinity regions (HNARs). HNARs are spanning over 600 bp, featuring high in vivo and predicted in vitro nucleosome occupancy and high predicted propeller twist DNA shape value. We suggest a two-step nucleosome destabilization-depletion model, in which the same intrinsic DNA properties of HNAR promote both high nucleosome occupancy and differential binding of TFs. In the first step, already before ZGA, Pou5f3 and Nanog destabilize nucleosomes at HNAR centers genome-wide. In the second step, post-ZGA, Nanog, Pou5f3, and SoxB1 maintain open chromatin state on the subset of HNARs, acting synergistically. Nanog binds to the HNAR center, whereas the Pou5f3 stabilizes the flanks. The HNAR model will provide a useful tool for genome regulatory studies in a variety of biological systems.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.240572.118.
- Received June 11, 2018.
- Accepted January 16, 2019.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
