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bioRxiv · 10.1101/2022.08.05.502932

Time-resolved analysis of Wnt-signaling reveals β-catenin temporal genomic repositioning and cell type-specific plastic or elastic chromatin responses

Pagella, P.·Soderholm, S.·Nordin, A.·Zambanini, G.·Jauregi-Miguel, A.·Cantu, C.
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Abstract

Wnt signaling orchestrates gene expression via its effector {beta}-catenin. Whether {beta}-catenin targets genomic regions simultaneously or in a temporal fashion, and how this impacts the chromatin dynamics to modulate cell behavior, is currently unknown. Here we find that {beta}-catenin binds different loci at each time-point after stimulation, implying that the definition of Wnt-targets is fundamentally temporal. This process is intrinsically cell-type specific. In fact, Wnt/{beta}-catenin progressively shapes the chromatin of human embryonic stem cells consistent with their mesodermal differentiation: we call this genomic response plastic. In embryonic kidney cells, on the other hand, Wnt/{beta}-catenin drives a transient chromatin opening, followed by a re-establishment of the pre-stimulation state: a response that we define elastic. Finally, the Wnt-induced transient chromatin opening requires {beta}-catenin, suggesting a previously unappreciated pioneering role for this molecule. We submit that the plastic-vs-elastic behavior constitutes part of the mechanism explaining how Wnt/{beta}-catenin drives divergent cell-fate decisions during development and homeostasis.

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Pagella, P., Soderholm, S., Nordin, A., Zambanini, G., Jauregi-Miguel, A., Cantu, C.. 2022-08-05. Time-resolved analysis of Wnt-signaling reveals β-catenin temporal genomic repositioning and cell type-specific plastic or elastic chromatin responses. https://doi.org/10.1101/2022.08.05.502932

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