NEGATIVE REGULATION OF VIRAL ENHANCERS IN UNDIFFERENTIATED EMBRYONIC STEM-CELLS

NEGATIVE REGULATION OF VIRAL ENHANCERS IN UNDIFFERENTIATED EMBRYONIC STEM-CELLS
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DOI:
10.1016/0092-8674(85)90109-6
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发表时间:
1985-01-01
期刊:
影响因子:
64.5
通讯作者:
LANE, DP
LANE, DP
中科院分区:
生物学1区
文献类型:
--
作者:
GORMAN, CM;RIGBY, PWJ;LANE, DP

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许多病毒基因组,包括SV 40和MuLV的基因组,在未分化的胚胎癌(EC)细胞中不能有效表达,但在分化的衍生物中表达。这种调节似乎是在转录水平。我们已经使用DNA介导的基因转移来分析几种病毒启动子在EC细胞中的功能。我们发现,SV 40早期启动子有效地工作在一个增强子独立的方式转染到未分化的细胞。引人注目的是,MSV的LTR中的启动子在这样的细胞中不起作用;但是当上游序列,包括增强子,被缺失时,表达增强。用MSV的增强子替换SV 40的增强子导致这些细胞中SV 40早期启动子的失活。我们认为未分化的细胞中含有一种反式作用调节因子,它通过与病毒增强子相互作用来降低转录。
Many viral genomes, including those of SV40 and MuLV, are not efficiently expressed in undifferentiated embryonal carcinoma (EC) cells but are expressed in differentiated derivatives. This regulation appears to be at the level of transcription. We have used DNA-mediated gene transfer to analyze the function of several viral promoters in EC cells. We show that the SV40 early promoter works efficiently in an enhancer-independent fashion following transfection into undifferentiated cells. Strikingly, the promoter in the LTR of MSV does not function in such cells; but when upstream sequences, including the enhancer, are deleted expression ensues. Replacement of the SV40 enhancer by that of MSV results in inactivation of the SV40 early promoter in these cells. We propose that the undifferentiated cells contain a trans-acting regulatory factor (or factors) that reduces transcription by interacting with viral enhancers.