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Chromatin Associated with TCR Allelic Exclusion1
Department of Immunology, Duke University Medical Center, Durham, NC 27710
To investigate chromatin control of TCR 
rearrangement and
allelic exclusion, we analyzed TCR chromatin structure in double
negative (DN) thymocytes, which are permissive for TCR
recombination, and in double positive (DP) thymocytes, which are
postallelic exclusion and nonpermissive for V to DJ
recombination. Histone acetylation mapping and DNase I sensitivity
studies indicate V and DJ 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
V acetylation and accessibility. The level of DP acetylation and
accessibility is minimal for five of six V segments studied but
remains substantial for one. Hence, the observed changes in V
chromatin structure appear sufficient to account for allelic exclusion
of many V segments. They may contribute to, but not by themselves
fully account for, allelic exclusion of others.
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