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.
Hawwari
Abbas
A
The Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bock
Cheryl
C
Krangel
Michael S
MS
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D002843:Chromatin; D006657:Histones; D016693:Receptors, Antigen, T-Cell, alpha-beta