Cell-to-Cell Variability in the Propensity to Transcribe Explains Correlated Fluctuations in Gene Expression

被引:53
作者
Sherman, Marc S. [1 ,2 ]
Lorenz, Kim [2 ]
Lanier, M. Hunter [3 ]
Cohen, Barak A. [2 ]
机构
[1] Washington Univ, Computat & Mol Biophys, St Louis, MO 63108 USA
[2] Washington Univ, Dept Genet, Ctr Genome Sci, St Louis, MO 63108 USA
[3] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63108 USA
关键词
D O I
10.1016/j.cels.2015.10.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Random fluctuations in gene expression lead to wide cell-to-cell differences in RNA and protein counts. Most efforts to understand stochastic gene expression focus on local (intrinisic) fluctuations, which have an exact theoretical representation. However, no framework exists to model global (extrinsic) mechanisms of stochasticity. We address this problem by dissecting the sources of stochasticity that influence the expression of a yeast heat shock gene, SSA1. Our observations suggest that extrinsic stochasticity does not influence every step of gene expression, but rather arises specifically from cell-to-cell differences in the propensity to transcribe RNA. This led us to propose a framework for stochastic gene expression where transcription rates vary globally in combination with local, gene-specific fluctuations in all steps of gene expression. The proposed model better explains total expression stochasticity than the prevailing ON-OFF model and offers transcription as the specific mechanism underlying correlated fluctuations in gene expression.
引用
收藏
页码:315 / 325
页数:11
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