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Sox2 levels configure the WNT response of epiblast progenitors responsible for vertebrate body formation

Robert Blassberg, Harshil Patel, Thomas Watson, Mina Gouti, Vicki Metzis, M Joaquina Delás, View ORCID ProfileJames Briscoe
doi: https://doi.org/10.1101/2020.12.29.424684
Robert Blassberg
1The Francis Crick Institute, London, United Kingdom, NW1 1AT
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Harshil Patel
1The Francis Crick Institute, London, United Kingdom, NW1 1AT
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Thomas Watson
1The Francis Crick Institute, London, United Kingdom, NW1 1AT
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Mina Gouti
3Stem Cell Modelling of Development & Disease Group, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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Vicki Metzis
1The Francis Crick Institute, London, United Kingdom, NW1 1AT
2Institute of Clinical Sciences, Imperial College London, London, W12 0NN
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M Joaquina Delás
1The Francis Crick Institute, London, United Kingdom, NW1 1AT
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James Briscoe
1The Francis Crick Institute, London, United Kingdom, NW1 1AT
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  • ORCID record for James Briscoe
  • For correspondence: james.briscoe@crick.ac.uk
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Abstract

WNT signalling has multiple roles. It maintains pluripotency of embryonic stem cells, assigns posterior identity in the epiblast and induces mesodermal tissue. We provide evidence that these distinct functions are conducted by the transcription factor SOX2, which adopts different modes of chromatin interaction and regulatory element selection depending on its level of expression. At high levels, SOX2 acts as a pioneer factor, displacing nucleosomes from regulatory elements with high affinity SOX2 binding sites and recruiting the WNT effector, TCF/β-catenin, to maintain pluripotent gene expression. Reducing SOX2 levels destabilises pluripotency and reconfigures SOX2/TCF/β-catenin occupancy to caudal epiblast expressed genes. These contain low-affinity SOX2 sites and are co-occupied by T/Bra and CDX. The loss of SOX2 allows WNT induced mesodermal differentiation. These findings define a role for Sox2 levels in dictating the chromatin occupancy of TCF/β-catenin and reveal how context specific responses to a signal are configured by the level of a transcription factor.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 30, 2020.
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Sox2 levels configure the WNT response of epiblast progenitors responsible for vertebrate body formation
Robert Blassberg, Harshil Patel, Thomas Watson, Mina Gouti, Vicki Metzis, M Joaquina Delás, James Briscoe
bioRxiv 2020.12.29.424684; doi: https://doi.org/10.1101/2020.12.29.424684
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Sox2 levels configure the WNT response of epiblast progenitors responsible for vertebrate body formation
Robert Blassberg, Harshil Patel, Thomas Watson, Mina Gouti, Vicki Metzis, M Joaquina Delás, James Briscoe
bioRxiv 2020.12.29.424684; doi: https://doi.org/10.1101/2020.12.29.424684

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