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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Conserved Cis-Regulatory Modules Control Robustness in Msx1 Expression at Single-Cell Resolution.

Keith W Vance1, Dan J Woodcock2, John E Reid3

  • 1Department of Biology and Biochemistry, University of Bath, United Kingdom Warwick Systems Biology Centre, University of Warwick, Coventry, United Kingdom School of Life Sciences, University of Warwick, Coventry, United Kingdom k.w.vance@bath.ac.uk g.koentges@warwick.ac.uk.

Genome Biology and Evolution
|September 6, 2015
PubMed
Summary

Gene expression noise is reduced by promoter DNA sequences, but cis-regulatory modules (CRMs) also control transcription rates and variability in single cells. CRMs act as filters to reduce noise, offering new insights into developmental gene regulation.

Keywords:
Msx1cis-regulatory modulepromoterrobustnesssingle-cell transcription

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Systems Biology

Background:

  • Transcription is a stochastic process, causing cell-to-cell variations in gene expression.
  • Essential genes require precise expression for cellular development, despite inherent biological noise.
  • The role of cis-regulatory modules (CRMs) in controlling transcriptional robustness in metazoans is largely unknown.

Purpose of the Study:

  • To investigate the function of conserved Msx1 CRMs and promoters in modulating single-cell transcription rates.
  • To understand how CRMs control transcriptional robustness and variability in gene expression.
  • To explore the relationship between promoter sequence, CRMs, and gene expression noise.

Main Methods:

  • Live cell imaging of transfected reporter genes in C2C12 mouse myoblasts.
  • Mathematical modeling and statistical inference to quantify transcription rates.
  • Analysis of conserved Msx1 CRMs and their associated promoters.

Main Results:

  • The relationship between mean expression and noise is determined solely by the promoter for the Msx1 gene.
  • CRMs modulate single-cell basal promoter rate distributions in a graded manner.
  • A novel CRM function, a transcriptional filter, was identified that reduces intracellular variability.

Conclusions:

  • CRMs play a crucial role in fine-tuning gene expression variability beyond promoter control.
  • The rheostatic model of CRM action is extended to single-cell resolution.
  • CRMs can independently regulate transcription rate and act as filters for noise, impacting developmental gene regulation.