| Co-Investigator(Kenkyū-buntansha) |
NAGATA Takuya TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (40303242)
MATSUDA Tadashi TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (20212219)
KISHI Hiroyuki TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (60186210)
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| Research Abstract |
1. Human Rag genomic locus ; Using a fragment of human RAG-1 cDNA, we isolated genomic DNA clones that contained either first or second exon of human RAG-1. We determined its exon/intron organization and the transcriptional start site. Similarly, we isolated genomic DNA clones that contains first or second exon of human RAG-2 and determined its exon/intron structure and the transcription initiation site for RAG-2. These led us to reveal, for the first time, the organization of human genomic RAG-1 and RAG-2 locus.
2. Regulation of human RAG transcription ; We characterized promoter regions for human RAG-1 and RAG-2, and revealed that the 5' promoter region of RAG-lwas indispensable for its basal promoter activity. On the contrary, the sequences between -63 to -107 of RAG-2 were shown to be essential for its promoter acticity, suggesting the regulation of RAG-1 and RAG-2 transcription may be controled by different transcriptional mechanisms.
3. Regulation of murine RAG-2 ; We found that the regulation of the mouse RAG-2 promoter activity is confered to 80 nucleotide upstream of RAG-2. We also found that a B cell-specific transcription protein, Pax-5, and a T cell-specific transcription protein, GATA-3, bind to the -80 to -17 nt region in B cells and T cells, respectively. These results indicate that distinct DNA binding proteins, Pax-5 and GATA-3, may regulate the murine RAG-2 promoter in B and T lineage cells, respectively.
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