title: Evidence of stage-specific element for germ-line transcription of the TCR alpha gene located upstream of J alpha49 locus.
abstract: T cell receptor (TCR) genes are rearranged and expressed in an ordered manner during T cell development. The basic mechanism regulating this stepwise DNA alteration is poorly understood. To address this issue, we explored the presence of a stage-specific element for germ-line transcription of the TCR alpha gene which is closely associated with gene rearrangement. First, germ-line transcription of the TCR alpha gene including the first segment of the J alpha locus, J alpha49, was delayed compared to that of the TCR beta gene in both normal and TCR-transgenic (Tg) mice. Furthermore, expression of this transcript could be induced by CD3epsilon-mediated signals in recombination-activating gene (RAG)-2-deficient mice. In TCR-Tg mice, the endogenous J alpha49 germ-line transcript could not yet be observed at the CD25+ double-negative (DN) stage when the TCR alpha transgene was expressed. Of immature T cell hybridomas derived from either scid thymocytes (CD25+ DN) or immature CD8-single positive (ISP) thymocytes, only the latter hybridoma expressed the J alpha49 germ-line transcript. These data indicate that the J alpha49 germ-line transcription occurs only at a specific developmental stage. Second, to determine which elements may be regulating stage specificity, we performed transient transfection analysis with a reporter gene and demonstrated that the upstream region of the J alpha49 locus possesses promoter activity in correlation with germ-line transcription in ISP-derived but not in SCID-derived hybridomas. These results indicate that the expression of TCR alpha germ-line transcripts is regulated in a stage-specific manner by a cis-element located within the J alpha locus.
authors.affiliation: Department of Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hozumi
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Habu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte; D018014:Gene Transfer Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta