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The establishment and maintenance of lymphocyte identity through gene silencing

Abstract

Cell identity is determined by selective gene activation and by the maintenance of other regulated genes in a silent state. Although activation mechanisms have been dissected in considerable depth, great strides towards an understanding of the molecular control of gene silencing have been made only recently. Molecular hallmarks of silent chromatin and proteins involved in its assembly and maintenance have been identified through genetic, cytological and biochemical studies in a variety of organisms. Immunologists are now beginning to use this knowledge to elucidate mechanisms underlying cell fate decisions and key developmental steps. This review surveys the current knowledge of gene silencing, with an emphasis on studies in lymphocytes that are advancing our general understanding of silencing mechanisms during development.

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Figure 1: Assembly of constitutively silent chromatin in S. pombe.
Figure 2: The Cd4 silencer is required for the establishment of silencing during maturation of double-positive thymocytes, but not for maintenance in CD8+ single-positive cells.
Figure 3: Hypothetical models by which CpG methylation can contribute to the propagation of a silent chromatin structure.

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Acknowledgements

I thank A. Fisher, R. Kingston, D. Littmann, M. Merkenschlager, S. Reiner and C. Wilson for valuable comments.

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Smale, S. The establishment and maintenance of lymphocyte identity through gene silencing. Nat Immunol 4, 607–615 (2003). https://doi.org/10.1038/ni0703-607

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