Trade-off between Responsiveness and Noise Suppression in Biomolecular System Responses to Environmental Cues
Figure 4
LPS-induced regulatory network driven by NF-κB, ATF3 and C/EBPδ transcription factors lies at the boundary of responsiveness and noise suppression.
(A) Schematic representation of the LPS-induced regulatory network. The network is comprised of overlapping positive and negative (coherent type 1 and type 2) feed-forward loops [24] in which LPS indirectly activates core transcription factors (NF-κB and ATF3) which regulate combinatorially target genes, such as the transcription factor C/EBPδ, interleukin 6 (IL6), tumor necrosis factor, alpha-induced protein 6 (TNFAIP6), Ccl3 chemokine and others [22]. Network notation is described in Figure 1. (B, C) The ξ and ρ, respectively, of the LPS-induced regulatory network as a function of the strengths of the LPS/TLR4/NFkB activation and the ATF3 repression (see Text S1). Each point on the heat maps represents the averaged ξ and ρ, respectively, over 100 random and noisy stimuli (see also Figure S13). The strengths of the LPS/TLR4/NFkB activation and the ATF3 repression are on a logarithmic scale. White lines represent WT parameters and their encircled intersection is the WT network.