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Structure of silent transcription intervals and noise characteristics of mammalian genes

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Original languageEnglish
Article number823
JournalMolecular Systems Biology
Volume11
Issue number7
DOIs
Publication statusPublished - 1 Jul 2015

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.

    Research areas

  • noise in mRNA counts, promoter cycle, single-cell time-lapse analysis, stochastic gene expression, transcriptional bursting

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