Structure of silent transcription intervals and noise characteristics of mammalian genes

Abstract

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.

Keywords

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