Identification of Transcriptional Factor(s) which regulates Ig gene expression

调节 Ig 基因表达的转录因子的鉴定

基本信息

批准号：
03670252
负责人：
NAKASHIMA Manabu
金额：
$ 1.28万
依托单位：
KYUSYU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Immunoglobulin heavy-chain (IgH) gene expression is regulated in a large part by the IgH gene intronic enhancer which is composed of certain protein-binding motifs. These motifs act as a DNA element which is important for the regulation of the IgH gene trasncription. Two of these motifs, HE2 and E6 in the human IgH gene intronic enhancer, are considered to affect the B cell-specific gene expression. E6 was found to function as a silencer in non-lymphoid cells. It is very important to identify the regulatory molecules acting on these elements and their in vivo function. To examine the true function of the HE2 and E6 motifs in vivo, we established transgenic mouse lines. A 3^'deletion mutant of the IgH gene intronic enhancer which includes an active HE2 motif showed almost the same degree of trnascriptional activity and tissue-specificity as the whole IgH gene intronic enhancer. Still more, using the luciferase-assay, it was confirmed at cellular level that the HE2 motif plays an important role in the tissue-specific activity of the IgH gene intronic enhancer. On the other hand, the E6 motif was in some non-B cells.In transgenic mice, the IgH gene intronic enhancer functioned not only in B-lymphocytes but also in choroid plexus cells which are similar to glial cells. This suggests the existence of common gene expression control mechanisms between the immune system and the nervous system.

免疫球蛋白重链（IGH）基因表达在很大的部分由IGH基因中内含子增强子调节，该增强子由某些蛋白质结合基序组成。这些基序是DNA元素，这对于调节IGH基因trasncription很重要。这些基序中的两个，即人IGH基因内含子增强子中的He2和E6，被认为会影响B细胞特异性基因表达。发现E6在非淋巴细胞中充当消音器。确定作用于这些元素及其体内功能的调节分子非常重要。为了检查体内HE2和E6基序的真实功能，我们建立了转基因小鼠系。 IGH基因内含子增强子的3^'缺失突变体，包括活跃的HE2基序显示几乎与整个IGH基因中内含子增强子的TRNASCRIPTINT活性和组织特异性几乎相同。更重要的是，使用荧光素酶测定，在细胞水平上证实，HE2基序在IGH基因内含子增强子的组织特异性活性中起重要作用。另一方面，E6基序是在某些非B细胞中。在转基因小鼠中，IGH基因内含子增强子不仅在B淋巴细胞中功能，而且在类似于神经胶质细胞的脉络丛细胞中。这表明免疫系统和神经系统之间存在共同基因表达控制机制。