The time-resolved genomic impact of Wnt/ß-catenin signaling.
Cell Syst
; 14(7): 563-581.e7, 2023 07 19.
Article
de En
| MEDLINE
| ID: mdl-37473729
ABSTRACT
Wnt signaling orchestrates gene expression via its effector, ß-catenin. However, it is unknown whether ß-catenin binds its target genomic regions simultaneously and how this impacts chromatin dynamics to modulate cell behavior. Using a combination of time-resolved CUT&RUN against ß-catenin, ATAC-seq, and perturbation assays in different cell types, we show that Wnt/ß-catenin physical targets are tissue-specific, ß-catenin "moves" on different loci over time, and its association to DNA accompanies changing chromatin accessibility landscapes that determine cell behavior. In particular, Wnt/ß-catenin progressively shapes the chromatin of human embryonic stem cells (hESCs) as they undergo mesodermal differentiation, a behavior that we define as "plastic." In HEK293T cells, on the other hand, Wnt/ß-catenin drives a transient chromatin opening, followed by re-establishment of the pre-stimulation state, a response that we define as "elastic." Future experiments shall assess whether other cell communication mechanisms, in addition to Wnt signaling, are ruled by time, cellular idiosyncrasies, and chromatin constraints. A record of this paper's transparent peer review process is included in the supplemental information.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Bêta-Caténine
/
Voie de signalisation Wnt
Limites:
Humans
Langue:
En
Journal:
Cell Syst
Année:
2023
Type de document:
Article
Pays d'affiliation:
Suède