Universal attenuators and their interactions with feedback loops in gene regulatory networks

Dianbo Liu, Luca Albergante, Timothy J. Newman (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
215 Downloads (Pure)


Using a combination of mathematical modelling, statistical simulation and large-scale data analysis we study the properties of linear regulatory chains (LRCs) within gene regulatory networks (GRNs). Our modelling indicates that downstream genes embedded within LRCs are highly insulated from the variation in expression of upstream genes, and thus LRCs act as attenuators. This observation implies a progressively weaker functionality of LRCs as their length increases. When analyzing the preponderance of LRCs in the GRNs of Escherichia coli K12 and several other organisms, we find that very long LRCs are essentially absent. In both E. coli and M. tuberculosis we find that four-gene LRCs are intimately linked to identical feedback loops that are involved in potentially chaotic stress response, indicating that the dynamics of these potentially destabilising motifs are strongly restrained under homeostatic conditions. The same relationship is observed in a human cancer cell line (K562), and we postulate that four-gene LRCs act as 'universal attenuators'. These findings suggest a role for long LRCs in dampening variation in gene expression, thereby protecting cell identity, and in controlling dramatic shifts in cell-wide gene expression through inhibiting chaos-generating motifs.

Original languageEnglish
Pages (from-to)7078-7093
Number of pages16
JournalNucleic Acids Research
Issue number12
Early online date1 Jun 2017
Publication statusPublished - 7 Jul 2017


  • feedback
  • genes
  • mathematics
  • tuberculosis


Dive into the research topics of 'Universal attenuators and their interactions with feedback loops in gene regulatory networks'. Together they form a unique fingerprint.

Cite this