THE HUMAN MYELIN BASIC-PROTEIN GENE IS INCLUDED WITHIN A 179-KILOBASE TRANSCRIPTION UNIT - EXPRESSION IN THE IMMUNE AND CENTRAL NERVOUS SYSTEMS
THE HUMAN MYELIN BASIC-PROTEIN GENE IS INCLUDED WITHIN A 179-KILOBASE TRANSCRIPTION UNIT - EXPRESSION IN THE IMMUNE AND CENTRAL NERVOUS SYSTEMS
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DOI：
10.1073/pnas.90.22.10695
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发表时间：
1993-11-15
影响因子：
11.1
通讯作者：
CAMPAGNONI, AT
中科院分区：
文献类型：
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作者：
PRIBYL, TM;CAMPAGNONI, CW;CAMPAGNONI, AT
从人少突胶质细胞瘤细胞系中分离出两个人Golli（在少突胶质细胞谱系中表达的基因）-MBP（髓鞘碱性蛋白）cDNA。对这些cDNA的分析使我们能够确定人类Golli-MBP基因的整个结构。Golli-MBP基因包含MBP转录单位，长度几乎等于179 kb，由10个外显子组成，其中7个外显子构成MBP基因。人Golli-MBP基因含有两个转录起始位点，每个位点产生一个可变剪接转录物家族。从第一转录起始位点产生至少两个Golli-MBP转录物，其含有基因的前三个外显子和一个或多个MBP外显子。第二个转录本家族仅包含MBP外显子并产生众所周知的MBP。在人类中，RNA印迹分析显示Golli-MBP转录本在胎儿胸腺、脾脏、人B细胞和巨噬细胞系以及胎儿脊髓中表达。这些发现清楚地将编码自身免疫原/致脑炎原MBP的外显子在中枢神经系统中的表达与免疫系统的细胞和组织通过Golli-MBP基因的正常表达联系起来。他们还确定了这个遗传位点，其中包括MBP基因，是物种之间的保守，提供了进一步的证据，MBP转录单位是Golli转录单位的一个组成部分，并表明这种结构安排是重要的遗传功能和/或这些基因的调节。
Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line. Analysis of these cDNAs has enabled us to determine the entire structure of the human Golli-MBP gene. The Golli-MBP gene, which encompasses the MBP transcription unit, is almost-equal-to 179 kb in length and consists of 10 exons, seven of which constitute the MBP gene. The human Golli-MBP gene contains two transcription start sites, each of which gives rise to a family of alternatively spliced transcripts. At least two Golli-MBP transcripts, containing the first three exons of the gene and one or more MBP exons, are produced from the first transcription start site. The second family of transcripts contains only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord. These findings clearly link the expression of exons encoding the autoimmunogen/encephalitogen MBP in the central nervous system to cells and tissues of the immune system through normal expression of the Golli-MBP gene. They also establish that this genetic locus, which includes the MBP gene, is conserved among species, providing further evidence that the MBP transcription unit is an integral part of the Golli transcription unit and suggest that this structural arrangement is important for the genetic function and/or regulation of these genes.