Universal attenuators and their interactions with feedback loops in gene regulatory networks.
Nucleic Acids Res
; 45(12): 7078-7093, 2017 Jul 07.
Article
en En
| MEDLINE
| ID: mdl-28575450
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
/
Linfocitos B
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Escherichia coli K12
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Redes Reguladoras de Genes
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Modelos Genéticos
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Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido