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 variable (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 recombination is shared in the rearrangement of all seven antigen receptor genes and is controlled by changes in chromatin structure, which regulate accessibility to the recombinase apparatus in a lineage- and stage-specific manner. These chromatin changes are linked to transcription of the locus in its unrearranged (germline) configuration. To understand how germline transcription of the TCRbeta-chain gene is regulated, we determined the structure of germline transcripts initiating near the Dbeta1 segment and identified a promoter within this region. The Dbeta1 promoter is active in the presence of the TCRbeta enhancer (Ebeta), and in this context, exhibits preferential activity in pro-T versus mature T-cell lines, as well as T- versus B-lineage specificity. These studies provide insight into the developmental regulation of TCRbeta germline transcription, one of the earliest steps in T-cell differentiation.
Doty
R T
RT
Departments of Medicine and Immunology, University of Washington, Puget Sound Blood Center, Seattle, WA, USA.
Xia
D
D
Nguyen
S P
SP
Hathaway
T R
TR
Willerford
D M
DM
D000818:Animals; D015152:Blotting, Northern; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D017353:Gene Deletion; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D019674:Genes, T-Cell Receptor beta; D016158:Genes, p53; D015698:Genomic Library; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000235:genetics / Q000276:immunology; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic; D045567:VDJ Recombinases
D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases