期刊
CELL
卷 122, 期 2, 页码 169-182出版社
CELL PRESS
DOI: 10.1016/j.cell.2005.06.006
关键词
-
资金
- NIGMS NIH HHS [R01 GM73058] Funding Source: Medline
HIV-1 Tat transactivation is vital for completion of the viral life cycle and has been implicated in determining proviral latency. We present an extensive experimental/computational study of an HIV-1 model vector (LTR-GFP-IRES-Tat) and show that stochastic fluctuations in Tat influence the viral latency decision. Low GFP/Tat expression was found to generate bifurcating phenotypes with clonal populations derived from single proviral integrations simultaneously exhibiting very high and near zero GFP expression. Although phenotypic bifurcation (PheB) was correlated with distinct genomic integration patterns, neither these patterns nor other extrinsic cellular factors (cell cycle/size, aneuploidy, chromatin silencing, etc.) explained PheB. Stochastic computational modeling successfully accounted for PheB and correctly predicted the dynamics of a Tat mutant that were subsequently confirmed by experiment. Thus, Tat stochastics appear sufficient to generate PheB (and potentially proviral latency), illustrating the importance of stochastic fluctuations in gene expression in a mammalian system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据