Evidence of stage-specific element for germ-line transcription of the TCR α gene located upstream of Jα49 locus
Katsuto Hozumi
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorYasushi Tanaka
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorTakehito Sato
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorAnne Wilson
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorSonoko Habu
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorKatsuto Hozumi
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorYasushi Tanaka
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorTakehito Sato
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorAnne Wilson
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorSonoko Habu
Department of Immunology, Tokai University School of Medicine, Isehara, Japan
Search for more papers by this authorAbstract
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 α gene which is closely associated with gene rearrangement. First, germ-line transcription of the TCR α gene including the first segment of the Jα locus, Jα49, was delayed compared to that of the TCR β gene in both normal and TCR-transgenic (Tg) mice. Furthermore, expression of this transcript could be induced by CD3ϵ-mediated signals in recombination-activating gene (RAG)-2-deficient mice. In TCR-Tg mice, the endogenous Jα49 germ-line transcript could not yet be observed at the CD25+ double-negative (DN) stage when the TCR α 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 Jα49 germ-line transcript. These data indicate that the Jα49 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 Jα49 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 α germ-line transcripts is regulated in a stage-specific manner by a cis-element located within the Jα locus.
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