Active maintenance of CD8+ T cell naivety through regulation of global genome architecture

Brendan E Russ; Adele Barugahare; Pushkar Dakle; Kirril Tsyganov; Sara Quon; Bingfei Yu; Jasmine Li; Jason K C Lee; Moshe Olshansky; Zhaohren He; Paul F Harrison; Michael See; Simone Nussing; Alison E Morey; Vibha A Udupa; Taylah J Bennett; Axel Kallies; Cornelis Murre; Phillipe Collas; David Powell; Ananda W Goldrath; Stephen J Turner

doi:10.1016/j.celrep.2023.113301

Active maintenance of CD8⁺ T cell naivety through regulation of global genome architecture

Cell Rep. 2023 Oct 31;42(10):113301. doi: 10.1016/j.celrep.2023.113301. Epub 2023 Oct 19.

Authors

Brendan E Russ¹, Adele Barugahare², Pushkar Dakle³, Kirril Tsyganov², Sara Quon⁴, Bingfei Yu⁴, Jasmine Li⁵, Jason K C Lee³, Moshe Olshansky³, Zhaohren He⁶, Paul F Harrison⁷, Michael See⁷, Simone Nussing⁸, Alison E Morey³, Vibha A Udupa³, Taylah J Bennett³, Axel Kallies⁹, Cornelis Murre⁶, Phillipe Collas¹⁰, David Powell⁷, Ananda W Goldrath⁴, Stephen J Turner¹¹

Affiliations

¹ Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia. Electronic address: brendan.russ@monash.edu.
² Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia; Bioinformatics Platform, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia.
³ Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia.
⁴ Department of Biological Sciences, University of California, San Diego, San Diego, CA, USA.
⁵ Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia; Department of Molecular Biology, University of California, San Diego, San Diego, CA, USA.
⁶ Department of Molecular Biology, University of California, San Diego, San Diego, CA, USA.
⁷ Bioinformatics Platform, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia.
⁸ Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
⁹ Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
¹⁰ Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
¹¹ Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia. Electronic address: stephen.j.turner@monash.edu.

Abstract

The differentiation of naive CD8⁺ T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8⁺ T cells. We observe that the architecture of the naive CD8⁺ T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation. Deletion of BACH2, or to a lesser extent, reducing SATB1 DNA binding, within naive CD8⁺ T cells results in a chromatin architecture more reminiscent of effector/memory states. This suggests that key transcription factors within naive CD8⁺ T cells act to restrain T cell differentiation by actively enforcing a unique naive chromatin state.

Keywords: CD8+ T cell; CP: Immunology; CP: Molecular biology; T cell memory; chromatin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes*
Cell Differentiation
Chromatin*
Immunologic Memory / genetics
Transcription Factors / genetics

Substances

Chromatin
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding