A) CpGs at the Cd8a and Cd8b promoters, as well as the E8V enhancer, are hypermethylated in DN and γδ T cells. Loss of this methylation due to DNMT1 deletion leads to inappropriate CD8 expression in these cells. MAZR associates with multiple regulatory elements in the Cd8 locus, and represses Cd8α/β transcription at the DN to DP transition, possibly through interactions with DNA methyltransferases. B) Downregulation of MAZR expression correlates with the relief of epigenetic Cd8α/β repression at the DP stage. Components of the SWI/SNF chromatin remodeling complex, and multiple enhancer elements (E8I, E8II, E8III, and E8V), contribute to the efficient activation of Cd8α/β expression in DP cells.