DNA architectural protein CTCF facilitates subset-specific chromatin interactions to limit the formation of memory CD8 + T cells.

Autor:	Quon S; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Yu B; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Russ BE; Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Tsyganov K; Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Bioinformatics Platform, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Nguyen H; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Toma C; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Heeg M; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Hocker JD; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Milner JJ; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA., Crotty S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA., Pipkin ME; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL 33458, USA., Turner SJ; Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia. Electronic address: stephen.j.turner@monash.edu., Goldrath AW; School of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: agoldrath@ucsd.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2023 May 09; Vol. 56 (5), pp. 959-978.e10. Date of Electronic Publication: 2023 Apr 10.
DOI:	10.1016/j.immuni.2023.03.017
Abstrakt:	Although the importance of genome organization for transcriptional regulation of cell-fate decisions and function is clear, the changes in chromatin architecture and how these impact effector and memory CD8 + T cell differentiation remain unknown. Using Hi-C, we studied how genome configuration is integrated with CD8 + T cell differentiation during infection and investigated the role of CTCF, a key chromatin remodeler, in modulating CD8 + T cell fates through CTCF knockdown approaches and perturbation of specific CTCF-binding sites. We observed subset-specific changes in chromatin organization and CTCF binding and revealed that weak-affinity CTCF binding promotes terminal differentiation of CD8 + T cells through the regulation of transcriptional programs. Further, patients with de novo CTCF mutations had reduced expression of the terminal-effector genes in peripheral blood lymphocytes. Therefore, in addition to establishing genome architecture, CTCF regulates effector CD8 + T cell heterogeneity through altering interactions that regulate the transcription factor landscape and transcriptome. Competing Interests: Declaration of interests A.W.G. is a member of the scientific advisory board of ArsenalBio. S.J.T. is a member of the scientific advisory board for Medicago, Inc., QC, Canada. No funding from Medicago or ArsenalBio was provided for this work. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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