Magor B G, Wilson M R, Miller N W, Clem L W, Middleton D L, Warr G W
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425.
J Immunol. 1994 Dec 15;153(12):5556-63.
The teleost fishes are among the earliest evolutionary lineages to have an Ig heavy chain (IgH) locus whose organization approximates that of mammals. To understand transcriptional control of the IgH locus in a teleost fish and to gain insight into the evolution of the control elements, the enhancer activity in the IgH locus of the channel catfish, Ictalurus punctatus, was investigated. Segments of the locus extending from upstream of the proximal JH gene to 2.5 kb downstream of the second transmembrane (TM2) exon of the mu gene were tested in transient transfection expression assays in murine myeloma and T cell lines, and in catfish B lymphoblastoid, monocyte-like, and putative T cell lines. In marked contrast to mammals, no enhancer activity was observed in the catfish JH to C mu intron, but strong enhancer activity (approaching that of the murine IgH intronic enhancer) was identified in a 1.8-kb segment that included the TM2 exon. This catfish enhancer was active in a B lineage-specific manner in both catfish and murine cells. It was not localized in a small core region, but appeared to contain multiple, dispersed cooperative elements rich in octamer- and mu E5-related motifs. Although the catfish IgH enhancer shares functional characteristics with the mammalian IgH intronic and 3' enhancers, its unusual organization does not permit any obvious inferences concerning evolutionary relationships between the catfish enhancer and any one of the murine IgH enhancers.
硬骨鱼是最早进化出免疫球蛋白重链（IgH）基因座的谱系之一，其结构与哺乳动物的相似。为了解硬骨鱼中IgH基因座的转录调控并深入了解调控元件的进化，研究了斑点叉尾鮰（Ictalurus punctatus）IgH基因座中的增强子活性。在鼠骨髓瘤和T细胞系以及斑点叉尾鮰B淋巴母细胞样、单核细胞样和假定的T细胞系中进行的瞬时转染表达试验中，测试了从近端JH基因上游延伸至μ基因第二个跨膜（TM2）外显子下游2.5 kb的基因座片段。与哺乳动物形成鲜明对比的是，在斑点叉尾鮰的JH至Cμ内含子中未观察到增强子活性，但在一个包含TM2外显子的1.8 kb片段中鉴定出了强增强子活性（接近鼠IgH内含子增强子的活性）。该斑点叉尾鮰增强子在斑点叉尾鮰和鼠细胞中均以B谱系特异性方式发挥作用。它并不局限于一个小的核心区域，而是似乎包含多个分散的协同元件，富含八聚体和μE5相关基序。尽管斑点叉尾鮰IgH增强子与哺乳动物IgH内含子和3'增强子具有功能特征，但它不同寻常的结构不允许就斑点叉尾鮰增强子与任何一种鼠IgH增强子之间的进化关系做出任何明显推断。
