Epigenomic features contributing to transcriptional priming in memory T cells. TCR and cytokine signaling induce large-scale chromatin remodeling during naive-to-effector T cell differentiation, resulting in transcriptional induction of general activation and effector gene programs. Upon resolution of inflammation and under homeostatic conditions, memory T cells maintain a specific part of these activation-associated transcriptional programs in an epigenetically primed state. At the genomic loci harboring these so-called “recall genes,” specific modifications to the local chromatin landscape at regulatory elements (i.e., promoters and enhancers) help prepare for rapid transcriptional activation upon secondary challenge of the memory T cell. Compared with the majority of NP genes, primed (P) genes can exhibit increased chromatin accessibility (i.e., through local loss of nucleosomes), reduced DNA methylation, altered histone modifications (e.g., increased histone methylation), paused RNAPII, recruitment of specific TFs, and changes in 3D genome topology (e.g., preformed promoter–enhancer contacts). All these molecular adaptations together prepare recall genes for near-instant transcriptional induction upon antigen reencounter, and can be maintained and propagated as memory T cells undergo homeostatic proliferation. TSS, transcription start site; RNAPII, RNA polymerase II; NP, nonprimed.