Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters.
Assembly of the gene encoding T cell receptor alpha (Tcra) is characterized by an orderly progression of primary and secondary V(alpha)-to-J(alpha) recombination events across the J(alpha) array, but the targeting mechanisms responsible for this progression are mostly unknown. Studies have shown that the T early-alpha promoter is important in targeting primary Tcra rearrangements. We found that T early-alpha and a previously unknown promoter associated with J(alpha)49 targeted primary recombination to discrete sets of constant alpha region (C(alpha))-distal J(alpha) segments and together directed nearly all normal primary recombination events. Furthermore, deletion of the T early-alpha promoter activated previously suppressed downstream promoters and stimulated primary rearrangement to centrally located J(alpha) segments. Central promoter derepression also occurred after primary rearrangement, thereby providing a mechanism to target secondary recombination events.
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Related Subject Headings
- Transcription, Genetic
- T-Lymphocytes
- Sequence Deletion
- Receptors, Antigen, T-Cell, alpha-beta
- Promoter Regions, Genetic
- Mice
- Immunology
- Humans
- Histones
- Germ Cells
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- T-Lymphocytes
- Sequence Deletion
- Receptors, Antigen, T-Cell, alpha-beta
- Promoter Regions, Genetic
- Mice
- Immunology
- Humans
- Histones
- Germ Cells