Chellappan S P, Nevins J R
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5878-82. doi: 10.1073/pnas.87.15.5878.
Adenovirus E1A-dependent trans-activation of viral transcription involves the utilization and alteration of multiple sequence-specific transcription factors. Cellular genes are also activated by E1A, one example being the immunoglobulin heavy-chain locus when assayed by transfection into fibroblast cells. We have explored the basis for the E1A-dependent activation of this cellular transcription unit. We demonstrate that the ATTTGCAT ("octamer") element found in the heavy-chain enhancer and promoter is a target for E1A trans-activation since this sequence can confer inducibility to the normally unresponsive simian virus 40 early promoter. In addition, adenovirus infection stimulates the DNA-binding activity of the ubiquitous octamer-specific factor, OTF-1, and we presume that this is the basis for the stimulation of transcription. Although there are no octamer elements in the adenovirus genome that are known to be important for transcription, there are octamer elements in the viral terminal repeat sequences. These elements bind the NFIII factor and are important for the initiation of DNA replication. Since the NFIII factor has been shown to be identical to OTF-1, we suggest that the stimulation of OTF-1/NFIII activity during an adenovirus infection may be important for efficient initiation of adenovirus DNA synthesis.
腺病毒E1A依赖的病毒转录反式激活涉及多种序列特异性转录因子的利用和改变。细胞基因也可被E1A激活,例如将其转染至成纤维细胞中进行检测时,免疫球蛋白重链基因座就会被激活。我们探究了E1A依赖激活该细胞转录单位的基础。我们证明,在重链增强子和启动子中发现的ATTTGCAT(“八聚体”)元件是E1A反式激活的靶点,因为该序列可赋予通常无反应的猿猴病毒40早期启动子诱导性。此外,腺病毒感染可刺激普遍存在的八聚体特异性因子OTF-1的DNA结合活性,我们推测这就是转录受到刺激的基础。虽然腺病毒基因组中不存在已知对转录很重要的八聚体元件,但在病毒末端重复序列中有八聚体元件。这些元件结合NFIII因子,对DNA复制的起始很重要。由于已证明NFIII因子与OTF-1相同,我们认为腺病毒感染期间OTF-1/NFIII活性的刺激可能对腺病毒DNA合成的有效起始很重要。