Epigenetic regulation of inducible gene expression in the immune system

Authors

  • Pek Siew Lim,

    1. Discipline of Biomedical Sciences, Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, Australia
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  • Jasmine Li,

    1. Discipline of Biomedical Sciences, Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, Australia
    2. Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia
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  • Adele F Holloway,

    Corresponding author
    1. Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
    • Discipline of Biomedical Sciences, Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, Australia
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  • Sudha Rao

    Corresponding author
    • Discipline of Biomedical Sciences, Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, Australia
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Correspondence: Dr Sudha Rao, Discipline of Biomedical Sciences, Faculty of Education, Science, Technology and Mathematics, The University of Canberra, Canberra, ACT 2601, Australia.Email: Sudha.Rao@canberra.edu.au

Dr Adele Holloway, Menzies Research Institute, Medical Sciences 1 Building, University of Tasmania, 17 Liverpool Street, Hobart TAS 7000, Australia. Email: A.F.Holloway@utas.edu.au

Senior author: Pek Siew Lim

Email: chloe.lim@canberra.edu.au

Summary

T cells are exquisitely poised to respond rapidly to pathogens and have proved an instructive model for exploring the regulation of inducible genes. Individual genes respond to antigenic stimulation in different ways, and it has become clear that the interplay between transcription factors and the chromatin platform of individual genes governs these responses. Our understanding of the complexity of the chromatin platform and the epigenetic mechanisms that contribute to transcriptional control has expanded dramatically in recent years. These mechanisms include the presence/absence of histone modification marks, which form an epigenetic signature to mark active or inactive genes. These signatures are dynamically added or removed by epigenetic enzymes, comprising an array of histone-modifying enzymes, including the more recently recognized chromatin-associated signalling kinases. In addition, chromatin-remodelling complexes physically alter the chromatin structure to regulate chromatin accessibility to transcriptional regulatory factors. The advent of genome-wide technologies has enabled characterization of the chromatin landscape of T cells in terms of histone occupancy, histone modification patterns and transcription factor association with specific genomic regulatory regions, generating a picture of the T-cell epigenome. Here, we discuss the multi-layered regulation of inducible gene expression in the immune system, focusing on the interplay between transcription factors, and the T-cell epigenome, including the role played by chromatin remodellers and epigenetic enzymes. We will also use IL2, a key inducible cytokine gene in T cells, as an example of how the different layers of epigenetic mechanisms regulate immune responsive genes during T-cell activation.

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