Manley N R, O'Connell M A, Sharp P A, Hopkins N
Center for Cancer Research, Massachusetts, Institute of Technology, Cambridge 02139.
J Virol. 1989 Oct;63(10):4210-23. doi: 10.1128/JVI.63.10.4210-4223.1989.
Nondefective Friend murine leukemia virus (MuLV) causes erythroleukemia when injected into newborn NFS mice, while Moloney MuLV causes T-cell lymphoma. Exchange of the Friend virus enhancer region, a sequence of about 180 nucleotides including the direct repeat and a short 3'-adjacent segment, for the corresponding region in Moloney MuLV confers the ability to cause erythroid disease on Moloney MuLV. We have used the electrophoretic mobility shift assay and methylation interference analysis to identify cellular factors which bind to the Friend virus enhancer region and compared these with factors, previously identified, that bind to the Moloney virus direct repeat (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987). We identified five binding sites for sequence-specific DNA-binding proteins in the Friend virus enhancer region. While some binding sites are present in both the Moloney and Friend virus enhancers, both viruses contain unique sites not present in the other. Although none of the factors identified in this report which bind to these unique sites are present exclusively in T cells or erythroid cells, they bind to three regions of the enhancer shown by genetic analysis to encode disease specificity and thus are candidates to mediate the tissue-specific expression and distinct disease specificities encoded by these virus enhancer elements.
无缺陷的Friend鼠白血病病毒(MuLV)注入新生NFS小鼠时会引发红白血病,而莫洛尼MuLV会引发T细胞淋巴瘤。将Friend病毒增强子区域(一段约180个核苷酸的序列,包括直接重复序列和短的3'相邻片段)与莫洛尼MuLV中的相应区域进行交换,可使莫洛尼MuLV获得引发红系疾病的能力。我们利用电泳迁移率变动分析和甲基化干扰分析来鉴定与Friend病毒增强子区域结合的细胞因子,并将这些因子与先前鉴定的与莫洛尼病毒直接重复序列结合的因子进行比较(N. A. Speck和D. Baltimore,《分子细胞生物学》7:1101 - 1110,1987)。我们在Friend病毒增强子区域鉴定出了序列特异性DNA结合蛋白的五个结合位点。虽然莫洛尼病毒和Friend病毒增强子中都存在一些结合位点,但两种病毒都含有对方所没有的独特位点。尽管本报告中鉴定出的与这些独特位点结合的因子没有一种仅存在于T细胞或红系细胞中,但它们与增强子的三个区域结合,遗传学分析表明这些区域编码疾病特异性,因此它们是介导这些病毒增强子元件所编码的组织特异性表达和不同疾病特异性的候选因子。