PT  - JOURNAL ARTICLE
AU  - Robert Blassberg
AU  - Harshil Patel
AU  - Thomas Watson
AU  - Mina Gouti
AU  - Vicki Metzis
AU  - M Joaquina Delás
AU  - James Briscoe
TI  - Sox2 levels configure the WNT response of epiblast progenitors responsible for vertebrate body formation
AID  - 10.1101/2020.12.29.424684
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.29.424684
4099  - http://biorxiv.org/content/early/2020/12/30/2020.12.29.424684.short
4100  - http://biorxiv.org/content/early/2020/12/30/2020.12.29.424684.full
AB  - 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 StatementThe authors have declared no competing interest.