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PreprintCC BY-NC-NDbioRxiv

WNT/β-catenin increases 3D chromatin mobility and reorganisation during posterior cell state transitions

3 more authors
  1. 1Imperial College London

Abstract

Chromatin mobility, the exploration of 3D conformations by the chromatin fibre, is implicated in transcription and DNA repair, and is thought to decrease progressively as cells differentiate. Here, combining live-cell 3D single-nucleosome tracking with genomic approaches, we show that chromatin mobility instead changes in a cell-type-specific manner, increasing as pluripotent cells acquire posterior fates. This is accompanied by 3D genome reorganisation, including loss of Polycomb-associated interactions and emergence of CDX2-associated interactions. Withdrawal of posteriorising WNT/{beta}-catenin signalling rapidly reduces chromatin mobility and partially restores Polycomb-associated chromatin interactions, while Cdx1/2/4-null cells fail to acquire these WNT/{beta}-catenin-dependent changes. Together, our findings establish chromatin mobility as a regulated property of cell state, with WNT/{beta}-catenin signalling and CDX factors acting as mediators that fine-tune the sampling of 3D chromatin interactions during cell state transitions.

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BibTeX
@misc{wurmser2026wntβcatenin,
  title = {{WNT/β-catenin increases 3D chromatin mobility and reorganisation during posterior cell state transitions}},
  author = {A. A. M. Wurmser and L. Mao and N. Markevych and G. G. Agsu and Y. Cao and Z. Zhang and M. Jonaitis and N. De Winter and B. D. Simons and P. M. Madapura and D. Holcman and T. E. Boroviak and D. Klenerman and S. Samarajiwa and S. Basu},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.05.756771},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756771v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - WNT/β-catenin increases 3D chromatin mobility and reorganisation during posterior cell state transitions
AU  - A. A. M. Wurmser
AU  - L. Mao
AU  - N. Markevych
AU  - G. G. Agsu
AU  - Y. Cao
AU  - Z. Zhang
AU  - M. Jonaitis
AU  - N. De Winter
AU  - B. D. Simons
AU  - P. M. Madapura
AU  - D. Holcman
AU  - T. E. Boroviak
AU  - D. Klenerman
AU  - S. Samarajiwa
AU  - S. Basu
PY  - 2026
DA  - 2026/10/05
PB  - bioRxiv
DO  - 10.64898/2026.10.05.756771
UR  - https://www.biorxiv.org/content/10.64898/2026.10.05.756771v1
AB  - Chromatin mobility, the exploration of 3D conformations by the chromatin fibre, is implicated in transcription and DNA repair, and is thought to decrease progressively as cells differentiate. Here, combining live-cell 3D single-nucleosome tracking with genomic approaches, we show that chromatin mobility instead changes in a cell-type-specific manner, increasing as pluripotent cells acquire posterior fates. This is accompanied by 3D genome reorganisation, including loss of Polycomb-associated interactions and emergence of CDX2-associated interactions. Withdrawal of posteriorising WNT/{beta}-catenin signalling rapidly reduces chromatin mobility and partially restores Polycomb-associated chromatin interactions, while Cdx1/2/4-null cells fail to acquire these WNT/{beta}-catenin-dependent changes. Together, our findings establish chromatin mobility as a regulated property of cell state, with WNT/{beta}-catenin signalling and CDX factors acting as mediators that fine-tune the sampling of 3D chromatin interactions during cell state transitions.
ER  -