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) 基因表达在很大程度上由 IgH 基因内含子增强子调节，该增强子由某些蛋白质结合基序组成。这些基序作为 DNA 元件，对于 IgH 基因转录的调节非常重要。其中两个基序，人类 IgH 基因内含子增强子中的 HE2 和 E6，被认为影响 B 细胞特异性基因表达。 E6被发现在非淋巴细胞中起到沉默剂的作用。识别作用于这些元件的调节分子及其体内功能非常重要。为了检查 HE2 和 E6 基序在体内的真实功能，我们建立了转基因小鼠品系。包含活性HE2基序的IgH基因内含子增强子的3''缺失突变体表现出与整个IgH基因内含子增强子几乎相同程度的转录活性和组织特异性。此外，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发挥重要作用。另一方面，E6基序存在于一些非B细胞中。在转基因小鼠中，IgH基因内含子增强子不仅在B淋巴细胞中起作用，而且在类似于神经胶质细胞的脉络丛细胞中起作用。这表明免疫系统和神经系统之间存在共同的基因表达控制机制。