ROLE OF AN ADENOVIRUS E2 PROMOTER BINDING-FACTOR IN E1A-MEDIATED COORDINATE GENE-CONTROL

ROLE OF AN ADENOVIRUS E2 PROMOTER BINDING-FACTOR IN E1A-MEDIATED COORDINATE GENE-CONTROL
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DOI:
10.1073/pnas.84.8.2180
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发表时间:
1987-04-01
影响因子:
11.1
通讯作者:
NEVINS, JR
NEVINS, JR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KOVESDI, I;REICHEL, R;NEVINS, JR

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腺病毒基因E1 A的产物负责刺激来自六个病毒启动子以及至少两个细胞启动子的转录。我们已经检测到的HeLa细胞因子,称为E2启动子结合因子(E2 F),似乎介导的病毒E2启动子的转录刺激。竞争实验表明,E2 F不识别和结合的E1 B,E3,E4,或主要的晚期启动子序列。此外,由E1 A刺激的三种另外的启动子,热休克蛋白70,β-珠蛋白和早期猿猴病毒40不结合E2 F。相反,该因子识别E1 A增强子中的序列,并且在E1 A增强子内是E2 F的重复结合位点。最后,来自E1 A增强子的单个E2 F结合位点可赋予小鼠β-CD增强子增加的转录。珠蛋白启动子,依赖于E1 A基因产物的作用。这种刺激需要E2 F的结合,因为结合位点的甲基化(其在体外阻断结合)降低了体内的转录刺激。因此,我们得出结论,E2 F可能是负责E1 A介导的E1 A基因的刺激以及E2基因,但不参与其他E1 A诱导型启动子的激活。
A product of the adenovirus gene E1A is responsible for the stimulation of transcription from six viral promoters as well as at least two cellular promoters. We have detected a HeLa cell factor, termed E2 promoter binding factor (E2F), that appears to mediate the transcriptional stimulation of the viral E2 promoter. Competition experiments revealed that E2F did not recognize and bind to the E1B, E3, E4, or major late promoter sequences. Furthermore, three additional promoters stimulated by E1A, heat shock protein 70, .beta.-globin, and early simian virus 40, do not bind E2F. In contrast, the factor does recognize sequences in the E1A enhancer, and within the E1A enhancer are duplicated binding sites for E2F. Finally, a single E2F binding site from the E1A enhancer can confer increased transcription to a mouse .beta.-globin promoter, dependent on the action of the E1A gene product. This stimulation requires binding of E2F since methylation of the binding site, which blocks binding in vitro, reduces transcription stimulation in vivo. We, therefore, conclude that E2F is likely to be responsible for the E1A-mediated stimulation of the E1A gene as well as the E2 gene but is not involved in the activation of the other E1A-inducible promoters.