Promoter decoding of transcription factor dynamics involves a trade‐off between noise and control of gene expression

Molecular Systems Biology

Anders S Hansen¹ 

[1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA

关键词: gene regulation;    gene expression noise;    microfluidics;    Msn2;    transcription factor dynamics;   

DOI  :  10.1038/msb.2013.56

来源: Wiley

【 摘 要 】

Abstract

Numerous transcription factors (TFs) encode information about upstream signals in the dynamics of their activation, but how downstream genes decode these dynamics remains poorly understood. Using microfluidics to control the nucleocytoplasmic translocation dynamics of the budding yeast TF Msn2, we elucidate the principles that govern how different promoters convert dynamical Msn2 input into gene expression output in single cells. Combining modeling and experiments, we classify promoters according to their signal-processing behavior and reveal that multiple, distinct gene expression programs can be encoded in the dynamics of Msn2. We show that both oscillatory TF dynamics and slow promoter kinetics lead to higher noise in gene expression. Furthermore, we show that the promoter activation timescale is related to nucleosome remodeling. Our findings imply a fundamental trade-off: although the cell can exploit different promoter classes to differentially control gene expression using TF dynamics, gene expression noise fundamentally limits how much information can be encoded in the dynamics of a single TF and reliably decoded by promoters.

Synopsis

The relationship between the dynamics of transcription factor activity, differential gene expression and noise in gene expression is analyzed in yeast to understand how different genetic programs can be activated by controlling the dynamics of a single transcription factor.

• The general principles that govern how promoters decode transcription factor (TF) dynamics are investigated.
• Multiple gene expression programs can be encoded in the dynamics of a single TF.
• Oscillatory TF dynamics leads to higher noise in gene expression.
• Promoters with slow activation inherently suffer from high noise in gene expression.

【 授权许可】

CC BY-NC-SA   
Copyright © 2013 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.