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

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• dc.contributor.author Stik, Grégoire
• dc.contributor.author Vidal, Enrique
• dc.contributor.author Barrero, Mercedes
• dc.contributor.author Cuartero, Sergi
• dc.contributor.author Vila-Casadesús, Maria
• dc.contributor.author Mendieta Esteban, Julen, 1992-
• dc.contributor.author Tian, Tian V.
• dc.contributor.author Choi, Jinmi
• dc.contributor.author Berenguer, Clara
• dc.contributor.author Abad, Amaya
• dc.contributor.author Borsari, Beatrice, 1992-
• dc.contributor.author Le Dily, François
• dc.contributor.author Cramer, Patrick
• dc.contributor.author Martí Renom, Marc A.
• dc.contributor.author Stadhouders, Ralph
• dc.contributor.author Graf, T. (Thomas)
• dc.date.accessioned 2020-09-30T10:11:35Z
• dc.date.issued 2020
• dc.description.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.
• dc.description.sponsorship We thank M. T. Kanemaki for the degron plasmids; R. Guigó’s laboratory, and S. Pérez-Lluch in particular, for the H3K27ac and H3K4me1 ChIP–seq, produced in the framework of the RNA-MAPS project (ERC-2011-AdG-294653-RNA-MAPS); Y. Cuartero for help with sequencing and CTCF ChIP–seq; C. Segura for help with immunofluorescence microscopy; the CRG Genomics and flow cytometry core facilities and the CRG-CNAG Sequencing Unit for sequencing; and members of T.G.’s laboratory for discussions. This work was supported by the European Research Council under the 7th Framework Programme FP7/2007-2013 (ERC Synergy Grant 4D-Genome, grant agreement 609989, to T.G. and M.A.M.-R.), the Ministerio de Educación y Ciencia (SAF.2012-37167, to T.G., and BFU2017-85926-P, to M.A.M.-R.), the AGAUR (to T.G.) and the Marató TV3 (201611) (to M.A.M.-R.). P.C. was supported by the Deutsche Forschungsgemeinschaft (SFB860, SPP1935, EXC 2067/1-390729940), the European Research Council (advanced investigator grant TRANSREGULON, grant agreement no. 693023) and the Volkswagen Foundation.
• dc.format.mimetype application/pdf
• dc.identifier.citation Stik G, Vidal E, Barrero M, Cuartero S, Vila-Casadesús M, Mendieta-Esteban J, Tian TV, Choi J, Berenguer C, Abad A, Borsari B, le Dily F, Cramer P, Marti-Renom MA, Stadhouders R, Graf T. CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response. Nat Genet. 2020; 52(7):655-61. DOI: 10.1038/s41588-020-0643-0
• dc.identifier.doi http://dx.doi.org/10.1038/s41588-020-0643-0
• dc.identifier.issn 1061-4036
• dc.identifier.uri http://hdl.handle.net/10230/45357
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Genet. 2020; 52(7):655-61
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/294653
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/693023
• dc.rights © Springer Nature Publishing AG Stik G, Vidal E, Barrero M, Cuartero S, Vila-Casadesús M, Mendieta-Esteban J, Tian TV, Choi J, Berenguer C, Abad A, Borsari B, le Dily F, Cramer P, Marti-Renom MA, Stadhouders R, Graf T. CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response. Nat Genet. 2020; 52(7):655-61. DOI: 10.1038/s41588-020-0643-0 [http://dx.doi.org/10.1038/s41588-020-0643-0]
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Epigenomics
• dc.subject.keyword Functional genomics
• dc.subject.keyword Gene regulation
• dc.subject.keyword Immunology
• dc.title CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion