T cells are essential for mounting defense against various pathogens and malignantly transformed cells. Thy-mic development and peripheral T cell differentiation are highly orchestrated biological processes that require precise gene regulation. Higher-order genome organization on multiple scales, in the form of chromatin loops, topologically associating domains and compartments, provides pivotal control of T cell gene expression. CTCF and the cohesin machinery are ubiquitously expressed architectural proteins responsible for establishing chromatin structures. Recent studies indicate that transcription factors, such as T lineage-defining Tcf1 and TCR-induced Batf, may have intrinsic ability and/or engage CTCF to shape chromatin architecture. In this article, we summarize current knowledge on the dynamic changes in genome topology that underlie normal or leukemic T cell development, CD4+ helper T cell differentiation, and CD8+ cytotoxic T cell functions. The knowledge lays a solid foundation for elucidating the causative link of spatial chromatin configuration to transcriptional and functional output in T cells. ? 2022 by The American Association of Immunologists.
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