Binding of Thymic Factors to the Conserved Decanucleotide Promoter Element of the T-Cell Receptor VβGene is Developmentally Regulated and is Absent in SCID Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-09, Vol.88 (18), p.8131-8135
• Main Authors: Lanier, E. Randall, Brown, Renee M., Kraig, Ellen
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Base Sequence; Biological and medical sciences; Cell lines; DNA; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Genes; Genetic loci; Immunologic Deficiency Syndromes - genetics; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Promoter regions; Promoter Regions, Genetic; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell, alpha-beta; Spleen; T cell antigen receptors; T lymphocytes; Thymus Extracts - metabolism; Thymus Gland - cytology; Thymus Gland - embryology; Thymus Gland - physiology; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.18.8131

The gene segments encoding the β chain of the T-cell antigen receptor undergo rearrangement in a precise developmental order: a Dβgene segment joins to a Jβgene segment prior to the rearrangement of a Vβgene segment to join the D/Jβfusion. Current evidence suggests that the rearrangement of Vβis restricted to T cells, whereas D-to-Jβrearrangements may occur in both B and T cells. Thus, the T-cell specificity seems to be regulated by the Vβcoding region or its 5' flanking sequence. In support of this hypothesis, evidence is provided for thymus-specific factors that bind a highly conserved 10-base-pair (decamer) sequence that is an essential promoter element in mouse and human Vβgenes. The presence of decamer-binding activities was assayed by gel mobility-shift analysis using protein extracts from thymus, spleen, and nonlymphoid organs of adult mice. Two shifted complexes, designated T2 and T3, were seen only when the decamer was incubated with extracts from thymus. When extracts from mice of various gestational ages were tested for decamer-binding activity, one of the thymus-specific complexes, T2, was first detected at day 16; this coincides with the time of initial activation of the Vβlocus. No decamer-binding activity was detected in extracts prepared from the thymuses of SCID (severe combined immunodeficiency) mice, which characteristically fail to rearrange these genes. Moreover, neither T2 nor T3 was detectable with extracts from spleen or from two T-cell lines that express the β chain; this suggests that the presence of these two complexes is not absolutely required for transcription of the T-cell receptor β locus. We conclude that there are tissue-specific and developmentally regulated factors that form complexes with the decamer sequence 5' of Vβ; these may represent initiation factors that control the activation of germ-line T-cell receptor Vβgenes for transcription and/or rearrangement.