Chromatin condensation via the condensin II complex is required for peripheral T-cell quiescence

• Published in: The EMBO journal 2011-01, Vol.30 (2), p.263-276
• Main Authors: Rawlings, Jason S, Gatzka, Martina, Thomas, Paul G, Ihle, James N
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Animals; Base Sequence; Blotting, Western; Cell Proliferation; Cellular biology; Chromatin; Chromatin Assembly and Disassembly - immunology; Chromatin Assembly and Disassembly - physiology; Chromatin Immunoprecipitation; condensin; cytokine signalling; Cytokines; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - metabolism; epigenetics; Fluorescent Antibody Technique; Gene Expression Regulation - immunology; Immunity, Cellular - immunology; Immunology; Interleukin-2 - metabolism; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron, Transmission; Molecular biology; Molecular Sequence Data; Multiprotein Complexes - metabolism; Promoter Regions, Genetic - genetics; quiescence; Receptors, Antigen, T-Cell - metabolism; Sequence Analysis, DNA; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2010.314

Naive T cells encountering their cognate antigen become activated and acquire the ability to proliferate in response to cytokines. Stat5 is an essential component in this response. We demonstrate that Stat5 cannot access DNA in naive T cells and acquires this ability only after T‐cell receptor (TCR) engagement. The transition is not associated with changes in DNA methylation or global histone modification but rather chromatin decondensation. Condensation occurs during thymocyte development and proper condensation is dependent on kleisin‐β of the condensin II complex. Our findings suggest that this unique chromatin condensation, which can affect interpretations of chromatin accessibility assays, is required for proper T‐cell development and maintenance of the quiescent state. This mechanism ensures that cytokine driven proliferation can only occur in the context of TCR stimulation. Peripheral T cells respond to the cytokine IL‐2 only after priming by T‐cell receptor‐specific antigens, which is shown to allow DNA binding of IL‐2‐activated Stat5. Surprisingly, quiescent T cells restrict Stat5 access not by histone or DNA modification, but rather by condensin‐mediated chromatin compaction.