E protein binding at the Tcra enhancer promotes Tcra repertoire diversity.
V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins are known regulators of DP thymocyte development and have three identified binding sites in Eα. To understand the contribution of E proteins to Eα function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of αβ T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the Jα array, along with dysregulated primary and impaired secondary Vα-Jα rearrangement. Eα E protein binding increases Tcra locus accessibility and regulates TCRα recombination, thus directly promoting Tcra repertoire diversity.
Duke Scholars
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Related Subject Headings
- V(D)J Recombination
- Transcription Factors
- Thymocytes
- Receptors, Antigen, T-Cell, alpha-beta
- Protein Binding
- Enhancer Elements, Genetic
- 3204 Immunology
- 3105 Genetics
- 3101 Biochemistry and cell biology
- 1108 Medical Microbiology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- V(D)J Recombination
- Transcription Factors
- Thymocytes
- Receptors, Antigen, T-Cell, alpha-beta
- Protein Binding
- Enhancer Elements, Genetic
- 3204 Immunology
- 3105 Genetics
- 3101 Biochemistry and cell biology
- 1108 Medical Microbiology