Epigenetic regulation of inducible gene expression in the immune system

• Published in: Immunology 2013-07, Vol.139 (3), p.285-293
• Main Authors: Lim, Pek Siew, Li, Jasmine, Holloway, Adele F, Rao, Sudha
• Format: Article
• Language: English
• Subjects: Cell activation; Chromatin; Chromatin - metabolism; Enzymes; Epigenetics; Epigenomics; Gene expression; Gene Expression Regulation; genomics; Humans; Kinases; Lymphocyte Activation; Lymphocytes; Review; T cells; T-Lymphocytes - metabolism; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; transcription factors/gene regulation
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12100

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.