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

## TL;DR

This study reveals how gene transcription in mammals is controlled by promoter cycles and how TATA box genes produce more noise in gene expression.

## Contribution

The paper introduces a new understanding of transcriptional bursting by linking promoter cycle complexity to intrinsic noise in gene expression.

## Key findings

- Endogenous promoters typically have five rate-limiting steps during silent intervals, while synthetic promoters have only one.
- Promoters with TATA boxes exhibit simplified two-state cycles and higher intrinsic noise in gene expression.
- Transcriptional bursting patterns influence genome-wide noise levels observed in single-cell RNA-seq data.

## 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.