title: BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.
abstract: T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. In naive cells, this prevented TCR-driven induction of genes associated with terminal differentiation. Upon effector differentiation, reduced expression of BACH2 and its phosphorylation enabled unrestrained induction of TCR-driven effector programs.
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.|Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Rahul
authors.initials: R
authors.lastname: Roychoudhuri
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.|Medical Scientist Training Program, Ohio State University College of Medicine, Columbus, OH., USA.
authors.forename: David
authors.initials: D
authors.lastname: Clever
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD., USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Systems Biology Center, NHLBI, NIH, Bethesda, MD., USA.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Wakabayashi
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD., USA.
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Quinn
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Klebanoff
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Madhusudhanan
authors.initials: M
authors.lastname: Sukumar
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Eil
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Zhiya
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD., USA.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Palmer
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Jenny H
authors.initials: JH
authors.lastname: Pan
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Shashank J
authors.initials: SJ
authors.lastname: Patel
authors.affiliation: Institute for Infection & Immunity, St. George's University of London, London, UK.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Macallan
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fabozzi
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD., USA.
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Shih
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD., USA.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.affiliation: Systems Biology Center, NHLBI, NIH, Bethesda, MD., USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD., USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Okkenhaug
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD., USA.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.affiliation: National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD., USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016759:Oncogene Protein p65(gag-jun); D015398:Signal Transduction / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D016759:Oncogene Protein p65(gag-jun); D018808:Transcription Factor AP-1