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research article

Structure of silent transcription intervals and noise characteristics of mammalian genes

Zoller, Benjamin  
•
Nicolas, Damien Lionel  
•
Molina, N.
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2015
Molecular Systems Biology

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.

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Type
research article
DOI
10.15252/msb.20156257
Web of Science ID

WOS:000358788900008

PubMed ID

26215071

Author(s)
Zoller, Benjamin  
Nicolas, Damien Lionel  
Molina, N.
Naef, Felix  
Date Issued

2015

Publisher

Nature / European Molecular Biology Organization

Published in
Molecular Systems Biology
Volume

11

Issue

7

Start page

823

End page

823

Subjects

noise in mRNA counts

•

promoter cyclep

•

single‐cell time‐lapse analysis

•

stochastic gene expression

•

transcriptional bursting

Editorial or Peer reviewed

NON-REVIEWED

Written at

EPFL

EPFL units
UPNAE  
Available on Infoscience
August 24, 2015
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/117286
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