CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response
2020 | journal article; research paper
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CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response
Stik, G.; Vidal, E.; Barrero, M.; Cuartero, S.; Vila-Casadesús, M.; Mendieta-Esteban, J. & Tian, T. V. et al. (2020)
Nature Genetics, 52(7) pp. 655-661. DOI: https://doi.org/10.1038/s41588-020-0643-0
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- Authors
- Stik, Grégoire; Vidal, Enrique; Barrero, Mercedes; Cuartero, Sergi; Vila-Casadesús, Maria; Mendieta-Esteban, Julen; Tian, Tian V.; Choi, Jinmi; Berenguer, Clara; Abad, Amaya; Borsari, Beatrice; le Dily, François; Cramer, Patrick ; Marti-Renom, Marc A.; Stadhouders, Ralph; Graf, Thomas
- Abstract
- 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.
- Issue Date
- 2020
- Journal
- Nature Genetics
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Cramer
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English