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Genome Research
Article
License: CC BY NC
Data sources: UnpayWall
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PubMed Central
Other literature type . 2012
License: CC BY NC
Data sources: PubMed Central
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Genome Research
Article . 2012 . Peer-reviewed
Data sources: Crossref
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Noise–mean relationship in mutated promoters

Authors: Hornung G; Bar-Ziv R; Rosin D; Tokuriki N; Tawfik DS; Oren M; Barkai N.;

Noise–mean relationship in mutated promoters

Abstract

Gene expression depends on the frequency of transcription events (burst frequency) and on the number of mRNA molecules made per event (burst size). Both processes are encoded in promoter sequence, yet their dependence on mutations is poorly understood. Theory suggests that burst size and frequency can be distinguished by monitoring the stochastic variation (noise) in gene expression: Increasing burst size will increase mean expression without changing noise, while increasing burst frequency will increase mean expression and decrease noise. To reveal principles by which promoter sequence regulates burst size and frequency, we randomly mutated 22 yeast promoters chosen to span a range of expression and noise levels, generating libraries of hundreds of sequence variants. In each library, mean expression (m) and noise (coefficient of variation, η) varied together, defining a scaling curve: η2 = b/m+ηext2. This relation is expected if sequence mutations modulate burst frequency primarily. The estimated burst size (b) differed between promoters, being higher in promoter containing a TATA box and lacking a nucleosome-free region. The rare variants that significantly decreased b were explained by mutations in TATA, or by an insertion of an out-of-frame translation start site. The decrease in burst size due to mutations in TATA was promoter-dependent, but independent of other mutations. These TATA box mutations also modulated the responsiveness of gene expression to changing conditions. Our results suggest that burst size is a promoter-specific property that is relatively robust to sequence mutations but is strongly dependent on the interaction between the TATA box and promoter nucleosomes.

Related Organizations
Keywords

Glycerol-3-Phosphate Dehydrogenase (NAD+), Binding Sites, Saccharomyces cerevisiae Proteins, Research, Glucose Transport Proteins, Facilitative, Saccharomyces cerevisiae, TATA Box, Nucleosomes, DNA-Binding Proteins, Gene Expression Regulation, Fungal, Mutation, RNA, Messenger, Heat-Shock Proteins, Transcription Factors

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
147
Top 1%
Top 10%
Top 1%
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