Zoller, BenjaminNicolas, Damien LionelMolina, N.Naef, Felix2015-08-242015-08-242015-08-24201510.15252/msb.20156257https://infoscience.epfl.ch/handle/20.500.14299/117286WOS:00035878890000826215071Mammalian 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.noise in mRNA countspromoter cyclepsingle‐cell time‐lapse analysisstochastic gene expressiontranscriptional burstingtext::journal::journal article::research article