Our study showed that lineage-determining transcription factors, such as EBF1 in B cell lymphoma and TCF1 in T cell leukaemia, shape 3D genome architecture by constraining cohesin movement. Cohesin in turn positions enhancers at the spatial centres of oncogenic loci and enables multi-enhancer regulation of key oncogenes. Together, these findings identify a unifying mechanism that links transcription factor activity, chromatin topology and oncogene control.
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References
Furlong, E. E. M. & Levine, M. Developmental enhancers and chromosome topology. Science 361, 1341–1345 (2018). A review article that presents recent advances in enhancer–promoter interactions.
Zhao, J. et al. Spatial promoter-enhancer hubs in cancer: organization, regulation, and function. Trends Cancer 9, 1069–1084 (2023). A review article that presents recent advances in multi-enhancer gene regulation in cancer.
Sofueva, S. et al. Cohesin-mediated interactions organize chromosomal domain architecture. EMBO J. 32, 3119–3129 (2013). This paper shows that CTCF and cohesin are required to maintain the organization of topologically associating domains.
Boettiger, A. & Murphy, S. Advances in chromatin imaging at kilobase-scale resolution. Trends Genet. 36, 273–287 (2020). A review article that presents recent advances in super-resolution imaging for chromatin folding mapping.
Zhou, Y. et al. EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells. Mol. Cell 82, 1003–1020-.e15 (2022). This paper reports de-repression of EBF1 as a driver of Noth-inhibitor-resistance acquisition in T cell leukaemia.
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This is a summary of: Zhou, Y. et al. Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation. Nat. Cell Biol. https://doi.org/10.1038/s41556-025-01827-2 (2025).
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Lineage-determining transcription factors EBF1 and TCF1 shape chromatin fibre folding. Nat Cell Biol 28, 11–12 (2026). https://doi.org/10.1038/s41556-025-01843-2
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DOI: https://doi.org/10.1038/s41556-025-01843-2
