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ABNORMAL RECOMBINATION ACTIVATING GENE (RAG) AND IMMUNO DEFICIENCY

异常重组激活基因 (RAG) 和免疫缺陷

基本信息

批准号：
11470169
负责人：
MURAGUCHI Atsushi
金额：
$ 8.58万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

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.

1.人Rag基因座;使用人RAG-1 cDNA的片段，我们分离出包含人RAG-1的第一或第二外显子的基因组DNA克隆。我们确定了它的外显子/内含子组织和转录起始位点。同样地，我们分离了包含人RAG-2的第一或第二外显子的基因组DNA克隆，并确定了其外显子/内含子结构和RAG-2的转录起始位点。这些使我们首次揭示了人类基因组RAG-1和RAG-2位点的组织。人RAG转录的调控：我们鉴定了人RAG-1和RAG-2的启动子区域，并揭示了RAG-1的5 '启动子区域是其基础启动子活性所必需的。相反，RAG-2的-63~-107之间的序列是其启动子活性所必需的，提示RAG-1和RAG-2的转录调控可能受不同的转录机制控制.小鼠RAG-2的调节;我们发现小鼠RAG-2启动子活性的调节被赋予RAG-2上游80个核苷酸。我们还发现B细胞特异性转录蛋白Pax-5和T细胞特异性转录蛋白GATA-3分别与B细胞和T细胞中的-80至-17 nt区域结合。这些结果表明，不同的DNA结合蛋白，Pax-5和加塔-3，可以调节鼠RAG-2启动子在B和T谱系细胞，分别。