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

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Liu D,Albergante L,Newman TJ

doi

10.1093/nar/gkx485

subject

Has Abstract

pub_date

2017-07-07 00:00:00

pages

7078-7093

issue

12

eissn

0305-1048

issn

1362-4962

pii

3859748

journal_volume

45

pub_type

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