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Peer-reviewedCC BYNature Communications

Loop extrusion by cohesin plays a role in enhancer-activated gene expression early in differentiation

  • Rosa J. Stolper1,2
  • Felice Ho‐Ching Tsang3,1
  • Emily Georgiades1
  • Lars L. P. Hanssen1
  • Edward Tunnacliffe1
  • Damien J. Downes1
  • Caroline L. Harrold1
  • Jim R. Hughes1
  • Robert A. Beagrie1,2
  • Benjamin Davies4,2
  • Mira T. Kassouf5
  • Douglas R. Higgs6,7
7 affiliations
  1. 1MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
  2. 2Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  3. 3Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  4. 4Francis Crick Institute, London, UK
  5. 5MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. [email protected]
  6. 6Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [email protected]
  7. 7MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. [email protected]
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Abstract

Enhancers and their target promoters often come into close physical proximity when activated. This may be explained by a variety of mechanisms, including cohesin-mediated chromatin loop extrusion. However, acute depletion of cohesin does not cause widespread changes in gene expression. We have tested the role of cohesin-mediated loop extrusion in gene expression at the mouse alpha-globin locus during erythropoiesis. Acute depletion of cohesin disrupts alpha-globin expression at early but not late stages of differentiation. Furthermore, when single or multiple CTCF sites, known to block cohesin, are placed between the alpha-globin enhancers and promoters, alpha-gene expression is disrupted. Importantly, the CTCF site's orientation is critical, suggesting that within this activated domain, in definitive erythroid cells, cohesin predominantly but not exclusively, translocates from the enhancers to the promoters. We find that loop extrusion does play an important role in establishing enhancer-promoter proximity and consequent expression of inducible genes during differentiation.

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Cite

BibTeXRIS
BibTeX
@article{stolper2026loop,
  title = {{Loop extrusion by cohesin plays a role in enhancer-activated gene expression early in differentiation}},
  author = {Rosa J. Stolper and Felice Ho‐Ching Tsang and Emily Georgiades and Lars L. P. Hanssen and Edward Tunnacliffe and Damien J. Downes and Caroline L. Harrold and Jim R. Hughes and Robert A. Beagrie and Benjamin Davies and Mira T. Kassouf and Douglas R. Higgs},
  journal = {Nature Communications},
  year = {2026},
  month = may,
  doi = {10.1038/s41467-026-73049-5},
  url = {https://doi.org/10.1038/s41467-026-73049-5},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Loop extrusion by cohesin plays a role in enhancer-activated gene expression early in differentiation
AU  - Rosa J. Stolper
AU  - Felice Ho‐Ching Tsang
AU  - Emily Georgiades
AU  - Lars L. P. Hanssen
AU  - Edward Tunnacliffe
AU  - Damien J. Downes
AU  - Caroline L. Harrold
AU  - Jim R. Hughes
AU  - Robert A. Beagrie
AU  - Benjamin Davies
AU  - Mira T. Kassouf
AU  - Douglas R. Higgs
PY  - 2026
DA  - 2026/05/26
JO  - Nature Communications
DO  - 10.1038/s41467-026-73049-5
UR  - https://doi.org/10.1038/s41467-026-73049-5
AB  - Enhancers and their target promoters often come into close physical proximity when activated. This may be explained by a variety of mechanisms, including cohesin-mediated chromatin loop extrusion. However, acute depletion of cohesin does not cause widespread changes in gene expression. We have tested the role of cohesin-mediated loop extrusion in gene expression at the mouse alpha-globin locus during erythropoiesis. Acute depletion of cohesin disrupts alpha-globin expression at early but not late stages of differentiation. Furthermore, when single or multiple CTCF sites, known to block cohesin, are placed between the alpha-globin enhancers and promoters, alpha-gene expression is disrupted. Importantly, the CTCF site's orientation is critical, suggesting that within this activated domain, in definitive erythroid cells, cohesin predominantly but not exclusively, translocates from the enhancers to the promoters. We find that loop extrusion does play an important role in establishing enhancer-promoter proximity and consequent expression of inducible genes during differentiation.
SN  - 2041-1723
ER  -