RT Journal Article
SR Electronic
T1 Pou5f3, SoxB1 and Nanog remodel chromatin on High Nucleosome Affinity Regions at Zygotic Genome Activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 344168
DO 10.1101/344168
A1 Marina Veil
A1 Lev Yampolsky
A1 Björn Grüning
A1 Daria Onichtchouk
YR 2018
UL http://biorxiv.org/content/early/2018/06/11/344168.abstract
AB The zebrafish embryo remains transcriptionally quiescent during the first 10 cell cycles. Only then Zygotic Genome Activation (ZGA) occurs and is accompanied by fast chromatin remodeling. At ZGA, homologs of mammalian stem cell transcription factors (TFs) Pou5f3/Oct4, Nanog and Sox19b bind to thousands of developmental enhancers to initiate transcription. So far, how these three ZGA TFs influence chromatin dynamics at ZGA has remained unresolved. To address this question, we analyzed before and after ZGA nucleosome positions in wild-type and Maternal-Zygotic (MZ) mutants for pou5f3 and nanog. 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 propeller twist DNA shape value. Just prior to ZGA, Pou5f3 and Nanog non-specifically compete with histones and reduce nucleosome occupancy on strong nucleosome positioning sequences genome-wide. After ZGA, specific binding of Nanog and Pou5f3/SoxB1 complex is necessary to maintain open chromatin state on more than 6,000 HNARs. Nanog binds to the strongest nucleosome positioning sequence within HNAR, while the Pou5f3/SoxB1 complex binds to the flanks of it. We suggest a model, where the same intrinsic DNA properties of HNAR promote both high nucleosome occupancy and differential binding of TFs. We hope that our model will provide a useful framework for genome regulatory studies in the variety of biological systems.