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 Genetics52(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

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