control of stochastic gene expression by host factors at the hiv promoter随机控制基因表达的宿主因素艾滋病毒启动子.pdfVIP

Control of Stochastic Gene Expression by Host Factors at the HIV Promoter 1 1 1 2,3 1,2,3 John C. Burnett , Kathryn Miller-Jensen , Priya S. Shah , Adam P. Arkin *, David V. Schaffer * 1 Department of Chemical Engineering and the Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, United States of America, 2 Department of Bioengineering, University of California Berkeley, Berkeley, California, United States of America, 3 Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America Abstract The HIV promoter within the viral long terminal repeat (LTR) orchestrates many aspects of the viral life cycle, from the dynamics of viral gene expression and replication to the establishment of a latent state. In particular, after viral integration into the host genome, stochastic fluctuations in viral gene expression amplified by the Tat positive feedback loop can contribute to the formation of either a productive, transactivated state or an inactive state. In a significant fraction of cells harboring an integrated copy of the HIV-1 model provirus (LTR-GFP-IRES-Tat), this bimodal gene expression profile is dynamic, as cells spontaneously and continuously flip between active (Bright) and inactive (Off) expression modes. Furthermore, these switching dynamics may contribute to the establishment and maintenance of proviral latency, because after viral integration long delays in gene expression can occur before viral transactivation. The HIV-1 promoter contains cis- acting Sp1 and NF-kB elements