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Structure of silent transcription intervals and noise characteristics of mammalian genes.

ABSTRACT: Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time-lapse recordings in mouse cells to identify minimal models of promoter cycles, which inform on the number and durations of rate-limiting steps responsible for refractory periods. The structure of promoter cycles is gene specific and independent of genomic location. Typically, five rate-limiting steps underlie the silent periods of endogenous promoters, while minimal synthetic promoters exhibit only one. Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two-state promoter cycles. Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome-wide in mammals, as revealed by single-cell RNA-seq. These findings have implications for basic transcription biology and shed light on interpreting single-cell RNA-counting experiments.

SUBMITTER: Zoller B

PROVIDER: S-EPMC4547851 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Structure of silent transcription intervals and noise characteristics of mammalian genes.

Zoller Benjamin B Nicolas Damien D Molina Nacho N Naef Felix F

Molecular systems biology 20150727 7

Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time-lapse recordings in mouse cells to identify minimal models of promoter cycles, which inform on the number and durations of rate-limiting steps responsible for refractory periods. The structure of promoter cycles is gene specific and inde ...[more]

PMID: 26215071

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Dataset Information

Structure of silent transcription intervals and noise characteristics of mammalian genes.

Publications

Structure of silent transcription intervals and noise characteristics of mammalian genes.

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