Henson J W
Molecular Neuro-oncology Laboratory, Massachusetts General Hospital, Charlestown 02129.
J Biol Chem. 1994 Jan 14;269(2):1046-50.
The regulation of glial-specific JC virus early gene expression was addressed by functional dissection of a previously uncharacterized form of the JC virus promoter (MH-1). The MH-1 promoter directed 31-fold higher reporter gene expression in U87MG glioma cells than in HeLa cells in a transient transfection assay. Transfection of promoter constructs containing proximal or proximal plus upstream regions revealed that reporter gene expression was activated by both proximal and tandem repeat regions in glioma cells. The proximal region contains a guanine-rich sequence, the GA box, which was found to regulate the promoter, and was recognized specifically by the transcription factor Sp1. The GA box is also present in the promoters of three glial-specific cellular genes. Together with paired AP-1 and NF-1 sites in the tandem repeats, the GA box is part of a motif that is conserved between several glial-specific promoters, and is thus a potential determinant of glial-specific gene expression. These results delineate the promoter regions required for activation of the MH-1 JC virus promoter, suggest a new determinant of glial specificity, and establish a model for the investigation of combinatorial activation of a glial-specific viral promoter.
通过对一种先前未被表征的JC病毒启动子形式（MH-1）进行功能剖析，研究了胶质细胞特异性JC病毒早期基因表达的调控。在瞬时转染实验中，MH-1启动子在U87MG胶质瘤细胞中指导的报告基因表达比在HeLa细胞中高31倍。转染含有近端或近端加上游区域的启动子构建体表明，报告基因表达在胶质瘤细胞中被近端和串联重复区域激活。近端区域包含一个富含鸟嘌呤的序列，即GA框，发现它可调节启动子，并被转录因子Sp1特异性识别。GA框也存在于三个胶质细胞特异性细胞基因的启动子中。与串联重复中的成对AP-1和NF-1位点一起，GA框是几个胶质细胞特异性启动子之间保守的基序的一部分，因此是胶质细胞特异性基因表达的潜在决定因素。这些结果描绘了激活MH-1 JC病毒启动子所需的启动子区域，提示了胶质细胞特异性的新决定因素，并建立了一个研究胶质细胞特异性病毒启动子组合激活的模型。
