Gene switching dynamics is a major source of randomness in genetic networks, also in the case of large concentrations of the transcription factors. In this work, we consider a common network motif - the positive feedback of a transcription factor on its own synthesis - and assess its response to extrinsic noises perturbing gene deactivation in a variety of settings where the network might operate. These settings are representative of distinct cellular types, abundance of transcription factors and ratio between gene switching and protein synthesis rates. By investigating noise-induced transitions among the different network operative states, our results suggest that gene switching rates are key parameters to shape network response to external perturbations, and that such response depends on the particular biological setting, i.e. the characteristic time scales and protein abundance. These results might have implications on our understanding of irreversible transitions for noise-related phenomena such as cellular differentiation. In addition these evidences suggest to adopt the appropriate mathematical model of the network in order to analyze the system consistently to the reference biological setting.

de Franciscis, S., Caravagna, G., Mauri, G., D’Onofrio, A. (2016). Gene switching rate determines response to extrinsic perturbations in the self-activation transcriptional network motif. SCIENTIFIC REPORTS, 6 [10.1038/srep26980].

Gene switching rate determines response to extrinsic perturbations in the self-activation transcriptional network motif

MAURI, GIANCARLO
Penultimo
;
2016

Abstract

Gene switching dynamics is a major source of randomness in genetic networks, also in the case of large concentrations of the transcription factors. In this work, we consider a common network motif - the positive feedback of a transcription factor on its own synthesis - and assess its response to extrinsic noises perturbing gene deactivation in a variety of settings where the network might operate. These settings are representative of distinct cellular types, abundance of transcription factors and ratio between gene switching and protein synthesis rates. By investigating noise-induced transitions among the different network operative states, our results suggest that gene switching rates are key parameters to shape network response to external perturbations, and that such response depends on the particular biological setting, i.e. the characteristic time scales and protein abundance. These results might have implications on our understanding of irreversible transitions for noise-related phenomena such as cellular differentiation. In addition these evidences suggest to adopt the appropriate mathematical model of the network in order to analyze the system consistently to the reference biological setting.
Articolo in rivista - Articolo scientifico
Gene switching; genetic networks; extrinsic noise
English
2016
6
26980
open
de Franciscis, S., Caravagna, G., Mauri, G., D’Onofrio, A. (2016). Gene switching rate determines response to extrinsic perturbations in the self-activation transcriptional network motif. SCIENTIFIC REPORTS, 6 [10.1038/srep26980].
File in questo prodotto:
File Dimensione Formato  
R149-srep26980.pdf

accesso aperto

Dimensione 2.61 MB
Formato Adobe PDF
2.61 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/129422
Citazioni
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
Social impact