Specialized T cell subsets mediate adaptive immunity in response to cytokine signaling and specific transcription factor activity. The epigenetic landscape of T cells has an important role in facilitating and establishing T cell fate decisions. Here, we review the interplay between transcription factors, histone modifications, DNA methylation and three-dimensional chromatin organization to define key elements of the epigenetic landscape in T cells. We introduce key technologies in the areas of sequencing, microscopy and proteomics that have enabled the multi-scale profiling of the epigenetic landscape. We highlight the dramatic changes of the epigenetic landscape as multipotent progenitor cells commit to the T cell lineage during development and discuss the epigenetic changes that favor the emergence of CD4+ and CD8+ T cells. Finally, we discuss the inheritance of epigenetic marks and its potential effects on immune responses as well as therapeutic strategies with potential for epigenetic regulation.
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