Sox2 levels regulate the chromatin occupancy of WNT mediators in epiblast progenitors responsible for vertebrate body formation
Author(s)
Type
Journal Article
Abstract
WNT signalling has multiple roles. It maintains pluripotency of embryonic stem cells, assigns posterior identity in the epiblast and induces mesodermal tissue. Here 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 displaces nucleosomes from regulatory elements with high-affinity SOX2 binding sites, recruiting the WNT effector TCF/β-catenin and maintaining pluripotent gene expression. Reducing SOX2 levels destabilizes 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.
Date Issued
2022-05
Date Acceptance
2022-03-29
Citation
Nature Cell Biology, 2022, 24 (5), pp.633-644
ISSN
1465-7392
Publisher
Nature Research
Start Page
633
End Page
644
Journal / Book Title
Nature Cell Biology
Volume
24
Issue
5
Copyright Statement
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The images or other
third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in a credit line to the material. If material is not included in
the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly
from the copyright holder. To view a copy of this license, visit http://creativecommons.
org/licenses/by/4.0/.
© The Author(s) 2022
Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The images or other
third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in a credit line to the material. If material is not included in
the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly
from the copyright holder. To view a copy of this license, visit http://creativecommons.
org/licenses/by/4.0/.
© The Author(s) 2022
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000799095000003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Cell Biology
DIFFERENTIATION
EMBRYONIC STEM-CELLS
EXPRESSION
GENES
Life Sciences & Biomedicine
LINEAGE
MOUSE
NANOG
NEUROMESODERMAL PROGENITORS
PLURIPOTENCY
Science & Technology
TRANSCRIPTION FACTORS
Publication Status
Published
Date Publish Online
2022-05-12