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The variable-diversity-joining (V-D-J) recombination and allelic exclusion, which drive selective T and B cell receptor expression, are tightly regulated by chromatin localization, DNA methylation, and activating histone marks such as acetylation and H3K4 trimethylation ( - CD4 - double negative (DN) stages via CD4 + CD8 + double positive (DP) to mature CD4 + or CD8 + single positive (SP) stages, the chromatin accessibility landscape undergoes consecutive remodeling with major changes marking T cell lineage commitment ( + or CD8 + SP T cells is, among others, driven by CD4 and CD8 regulatory elements, which are epigenetically regulated ( + T cell undergoes differentiation to either IFN--producing T helper type 1 (Th1) or IL-4-producing Th2 cells, the expression of the signature cytokines and master transcription factors is regulated by chromatin structure, where Th1-specific loci become enriched in activating histone marks while Th2-specific genes are enriched in suppressive histone marks in Th1 cells and vice versa ( Regulatory T (Treg) cells are a subpopulation of CD4 + T cells that restrain immune response