The time-resolved genomic impact of Wnt/β-catenin signaling

Pierfrancesco Pagella1, Simon Söderholm1, Anna Nordin1

  • 1Wallenberg Centre for Molecular Medicine, Linköping University, 58185 Linköping, Sweden; Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Faculty of Medicine and Health Sciences, Linköping University, 58185 Linköping, Sweden.

Cell Systems
|July 20, 2023
PubMed

Insights

Wnt/β-catenin binding dynamics at genomic targets are tissue-specific and time-dependent, influencing chromatin accessibility and cell behavior. This study reveals plastic and elastic responses in human embryonic stem cells and HEK293T cells, respectively.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cell Biology

Background:

  • Wnt signaling regulates gene expression through β-catenin.
  • The dynamic binding of β-catenin to genomic targets and its impact on chromatin are not well understood.

Purpose of the Study:

  • To investigate the temporal dynamics of β-catenin binding to genomic regions.
  • To understand how β-catenin-mediated chromatin changes influence cell behavior.
  • To characterize tissue-specific responses to Wnt signaling.

Main Methods:

  • Time-resolved CUT&RUN assay for β-catenin.
  • Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq).
  • Perturbation assays in various cell types.

Main Results:

  • Wnt/β-catenin physical targets are tissue-specific.
  • β-catenin exhibits dynamic binding to loci over time.
  • Chromatin accessibility landscapes change with β-catenin association, modulating cell behavior.
  • Human embryonic stem cells show a 'plastic' chromatin response during mesodermal differentiation.
  • HEK293T cells display an 'elastic' response with transient chromatin opening.

Conclusions:

  • Wnt/β-catenin binding dynamics are crucial for tissue-specific gene regulation and cell plasticity.
  • Cellular responses to Wnt signaling are influenced by time, cell type, and chromatin constraints.
  • Future research should explore these principles in other cell communication pathways.

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