Hiebert S W, Lipp M, 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. 1989 May;86(10):3594-8. doi: 10.1073/pnas.86.10.3594.
E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here we show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, we also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. We conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription.
E2F是一种细胞转录因子，可与腺病毒E2启动子中的两个位点结合。先前的实验表明E2F参与了E2基因的E1A依赖性反式激活，因为在腺病毒感染期间，活性E2F的水平与E2转录的增加同时显著升高，并且一个E2F结合位点可赋予异源启动子E1A诱导性。在此我们表明，E2F与人MYC基因P2启动子内的两个序列元件结合，这两个元件位于对启动子活性至关重要的区域内。MYC启动子可以以E1A依赖性方式被反式激活，定点诱变表明这些E2F元件对于反式激活至关重要。最后，我们还发现静止细胞的腺病毒感染会导致内源性MYC基因受到刺激。我们得出结论，E2F因子的激活可能负责病毒E2转录的激活，也负责E1A依赖性的MYC转录诱导。
