Promoter element for transcription of unrearranged T-cell receptor beta-chain gene in pro-T cells

The hallmark of T- and B-lymphocyte development is the rearrangement of var iable (V), diversity (D), and joining (J) segments of T-cell receptor (TCR) and immunoglobulin (Ig) genes to generate a diverse repertoire of antigen receptor specificities in the immune system. The process of V(D)J recombina tion is shared in the rearrangement of all seven antigen receptor genes and is controlled by changes in chromatin structure, which regulate accessibil ity to the recombinase apparatus in a lineage- and stage-specific manner. T hese chromatin changes are linked to transcription of the locus in its unre arranged (germline) configuration. To understand how germline transcription of the TCR beta-chain gene is regulated, we determined the structure of ge rmline transcripts initiating near the D beta 1 segment and identified a pr omoter within this region. The D beta 1 promoter is active in the presence of the TCR beta enhancer (E beta), and in this context, exhibits preferenti al activity in pro-T versus mature T-cell lines, as well as T- versus B-lin eage specificity. These studies provide insight into the developmental regu lation of TCR beta germline transcription, one of the earliest steps in T-c ell differentiation. (C) 1999 by The American Society of Hematology.