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在未分化的胚胎干细胞中对病毒增强剂的负调节

C M Gorman, P W Rigby, D P Lane

|September 1, 1985

概括

病毒基因表达在未分化胚胎癌 (EC) 细胞中受到限制. 在EC细胞中的转基因作用因子似乎通过与病毒增强剂相互作用来抑制病毒转录.

科学领域:

分子生物学分子生物学
病毒学病毒学
细胞生物学细胞生物学

背景情况:

病毒基因组表达在未分化的胚胎癌细胞 (EC) 和它们的分化对应细胞之间有所不同.
这种差异表达主要在转录水平上受到调节.
了解这些调节机制对于控制病毒基因活性至关重要.

研究的目的:

为了研究未分化的EC细胞中病毒促进体的功能活性.
确定负责差异性病毒基因表达的调节元件.
阐明细胞因子在调节病毒转录中的作用.

主要方法:

通过DNA介导的基因转移被用来在EC细胞中引入病毒促进体结构.
评估了Simian Virus 40 (SV40) 早期促销者的活性和小鼠肉瘤病毒 (MSV) 长终端重复 (LTR) 促销者的活性.
系统地分析了涉及增强元和上游序列的突变.

主要成果:

在未分化的EC细胞中,SV40早期促进体表现出高效,增强剂独立的功能.
在未分化的EC细胞中,MSV LTR促进体是非功能性的,但在删除包括增强体在内的上游序列后,表达得到恢复.
用MSV增强剂取代SV40增强剂导致这些细胞中SV40早期促进剂的失活.

结论:

不分化的EC细胞具有抑制病毒转录的转作用调节因子.
这一因素可能与病毒增强剂序列相互作用,以抑制基因表达.
这些发现表明,在多能干细胞中,病毒基因调节的新机制存在.

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