A change in the structure of Vβ chromatin associated with TCR β allelic exclusion

To investigate chromatin control of TCR β rearrangement and allelic exclusion, we analyzed TCR β chromatin structure in double negative (DN) thymocytes, which are permissive for TCR β recombination, and in double positive (DP) thymocytes, which are postallelic exclusion and nonpermissive for Vβ to DβJβ recombination. Histone acetylation mapping and DNase I sensitivity studies indicate Vβ and DβJβ segments to be hyperacetylated and accessible in DN thymocytes. However, they are separated from each other by hypoacetylated and inaccessible trypsinogen chromatin. The transition from DN to DP is accompanied by selective down-regulation of Vβ acetylation and accessibility. The level of DP acetylation and accessibility is minimal for five of six Vβ segments studied but remains substantial for one. Hence, the observed changes in Vβ chromatin structure appear sufficient to account for allelic exclusion of many Vβ segments. They may contribute to, but not by themselves fully account for, allelic exclusion of others.