A change in the structure of Vbeta chromatin associated with TCR beta allelic exclusion.
To investigate chromatin control of TCR beta rearrangement and allelic exclusion, we analyzed TCR beta chromatin structure in double negative (DN) thymocytes, which are permissive for TCR beta recombination, and in double positive (DP) thymocytes, which are postallelic exclusion and nonpermissive for Vbeta to DbetaJbeta recombination. Histone acetylation mapping and DNase I sensitivity studies indicate Vbeta and DbetaJbeta 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 Vbeta acetylation and accessibility. The level of DP acetylation and accessibility is minimal for five of six Vbeta segments studied but remains substantial for one. Hence, the observed changes in Vbeta chromatin structure appear sufficient to account for allelic exclusion of many Vbeta segments. They may contribute to, but not by themselves fully account for, allelic exclusion of others.
Tripathi
Rajkamal
R
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Jackson
Annette
A
Krangel
Michael S
MS
D000107:Acetylation; D000483:Alleles; D002843:Chromatin / Q000737:chemistry*; D003850:Deoxyribonuclease I / Q000737:chemistry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019674:Genes, T-Cell Receptor beta; D006657:Histones / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008957:Models, Genetic; D011233:Precipitin Tests; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014362:Trypsinogen / Q000737:chemistry
D002843:Chromatin; D006657:Histones; D007135:Immunoglobulin Variable Region; D014362:Trypsinogen; D003850:Deoxyribonuclease I