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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Trypsinogen
- Thymus Gland
- T-Lymphocytes
- Precipitin Tests
- Models, Genetic
- Immunology
- Immunoglobulin Variable Region
- Histones
- Genes, T-Cell Receptor beta
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Trypsinogen
- Thymus Gland
- T-Lymphocytes
- Precipitin Tests
- Models, Genetic
- Immunology
- Immunoglobulin Variable Region
- Histones
- Genes, T-Cell Receptor beta
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor