Regulation of T cell receptor α gene assembly by a complex hierarchy of germline Jα 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 a 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.