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 Resjournal_title
Nucleic acids researchauthors
Liu D,Albergante L,Newman TJdoi
10.1093/nar/gkx485subject
Has Abstractpub_date
2017-07-07 00:00:00pages
7078-7093issue
12eissn
0305-1048issn
1362-4962pii
3859748journal_volume
45pub_type
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