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Author Notes:

Author for correspondence (kondohh@cc.kyoto-su.ac.jp)

See publication for full list of author contributions.

We thank Paul J. Tesar and Jun Aruga for provision of the EpiSC line and anti-ZIC2 antibodies, respectively, and Carlos S. Moreno for discussions.

K.M. was a doctoral research fellow of Japan Society for the Promotion of Science.

The authors declare no competing or financial interests.

Subjects:

Research Funding:

This study was supported by Japan Society for the Promotion of Science Kakenhi Grants (P231147090, P23657007, P25113713 and P26251024 to H.K.) and Collaborative Research Grants of National Institute for Basic Biology.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Developmental Biology
  • ZIC2
  • POU3F1
  • OTX2
  • ESC
  • EpiSC
  • Mouse
  • IN-VIVO
  • PRIMED PLURIPOTENCY
  • FATE SPECIFICATION
  • PRIMITIVE STREAK
  • ENHANCER
  • CHROMATIN
  • PROTEIN
  • TRANSITION
  • DIFFERENTIATION
  • BIOTINYLATION

ChIP-seq analysis of genomic binding regions of five major transcription factors highlights a central role for ZIC2 in the mouse epiblast stem cell gene regulatory network

Tools:

Journal Title:

Development

Volume:

Volume 144, Number 11

Publisher:

, Pages 1948-1958

Type of Work:

Article | Final Publisher PDF

Abstract:

To obtain insight into the transcription factor (TF)-dependent regulation of epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic binding regions of five major TFs. Analysis of in vivo biotinylated ZIC2, OTX2, SOX2, POU5F1 and POU3F1 binding in EpiSCs identified several new features. (1) Megabase-scale genomic domains rich in ZIC2 peaks and genes alternate with those rich in POU3F1 but sparse in genes, reflecting the clustering of regulatory regions that act at short and long-range, which involve binding of ZIC2 and POU3F1, respectively. (2) The enhancers bound by ZIC2 and OTX2 prominently regulate TF genes in EpiSCs. (3) The binding sites for SOX2 and POU5F1 in mouse embryonic stem cells (ESCs) and EpiSCs are divergent, reflecting the shift in the major acting TFs from SOX2/POU5F1 in ESCs to OTX2/ZIC2 in EpiSCs. (4) This shift in the major acting TFs appears to be primed by binding of ZIC2 in ESCs at relevant genomic positions that later function as enhancers following the disengagement of SOX2/POU5F1 from major regulatory functions and subsequent binding by OTX2. These new insights into EpiSC gene regulatory networks gained from this study are highly relevant to early stage embryogenesis.

Copyright information:

© 2017. Published by The Company of Biologists Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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