Stik, GrégoireGrégoireStikVidal, EnriqueEnriqueVidalBarrero, MercedesMercedesBarreroCuartero, SergiSergiCuarteroVila-Casadesús, MariaMariaVila-CasadesúsMendieta-Esteban, JulenJulenMendieta-EstebanTian, Tian V.Tian V.TianChoi, JinmiJinmiChoiBerenguer, ClaraClaraBerenguerAbad, AmayaAmayaAbadBorsari, BeatriceBeatriceBorsarile Dily, FrançoisFrançoisle DilyCramer, PatrickPatrickCramerMarti-Renom, Marc A.Marc A.Marti-RenomStadhouders, RalphRalphStadhoudersGraf, ThomasThomasGraf2022-02-212022-02-212020https://resolver.sub.uni-goettingen.de/purl?gro-2/100150Three-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.enjournal_article10.1038/s41588-020-0643-032514124