CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response

Three-dimensional organization of the genome is important for transcriptional regulation1-7. In mammals, CTCF and the cohesin complex create submegabase structures with elevated internal chromatin contact frequencies, called topologically associating domains (TADs)8-12. Although TADs can contribute...

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Detalles Bibliográficos
Autores: Stik, Grégoire, Vidal, Enrique, Barrero, Mercedes, Cuartero, Sergi, Vila-Casadesús, Maria, Mendieta Esteban, Julen, 1992-, Tian, Tian V., Choi, Jinmi, Berenguer Balaguer, Clara, Abad, Amaya, Borsari, Beatrice, 1992-, Le Dily, François, Cramer, Patrick, Marti-Renom, Marc A., Stadhouders, Ralph, Graf, T. (Thomas)
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/45357
Acceso en línea:http://hdl.handle.net/10230/45357
http://dx.doi.org/10.1038/s41588-020-0643-0
Access Level:acceso abierto
Palabra clave:Epigenomics
Functional genomics
Gene regulation
Immunology
Descripción
Sumario:Three-dimensional organization of the genome is important for transcriptional regulation1-7. In mammals, CTCF and the cohesin complex create submegabase structures with elevated internal chromatin contact frequencies, called topologically associating domains (TADs)8-12. Although TADs can contribute to transcriptional regulation, ablation of TAD organization by disrupting CTCF or the cohesin complex causes modest gene expression changes13-16. In contrast, CTCF is required for cell cycle regulation17, embryonic development and formation of various adult cell types18. To uncouple the role of CTCF in cell-state transitions and cell proliferation, we studied the effect of CTCF depletion during the conversion of human leukemic B cells into macrophages with minimal cell division. CTCF depletion disrupts TAD organization but not cell transdifferentiation. In contrast, CTCF depletion in induced macrophages impairs the full-blown upregulation of inflammatory genes after exposure to endotoxin. Our results demonstrate that CTCF-dependent genome topology is not strictly required for a functional cell-fate conversion but facilitates a rapid and efficient response to an external stimulus.

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