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Stochastic expression dynamics of a transcription factor revealed by single-molecule noise analysis.

Abstract：

:Gene expression is inherently stochastic; precise gene regulation by transcription factors is important for cell-fate determination. Many transcription factors regulate their own expression, suggesting that autoregulation counters intrinsic stochasticity in gene expression. Using a new strategy, cotranslational activation by cleavage (CoTrAC), we probed the stochastic expression dynamics of cI, which encodes the bacteriophage λ repressor CI, a fate-determining transcription factor. CI concentration fluctuations influence both lysogenic stability and induction of bacteriophage λ. We found that the intrinsic stochasticity in cI expression was largely determined by CI expression level irrespective of autoregulation. Furthermore, extrinsic, cell-to-cell variation was primarily responsible for CI concentration fluctuations, and negative autoregulation minimized CI concentration heterogeneity by counteracting extrinsic noise and introducing memory. This quantitative study of transcription factor expression dynamics sheds light on the mechanisms cells use to control noise in gene regulatory networks.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Hensel Z,Feng H,Han B,Hatem C,Wang J,Xiao J

doi

10.1038/nsmb.2336

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

797-802

issue

8

eissn

1545-9993

issn

1545-9985

pii

nsmb.2336

journal_volume

19

pub_type

杂志文章

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