Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.
Bottom Line: The gene regulatory network (GRN) is the central decision-making module of the cell.BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response.BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation.
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom firstname.lastname@example.org.Show MeSH
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Mentions: Since a full eukaryotic transcriptional response typically requires >1 hr, we expect the ‘0.5 hr’ network to be similar to the ‘0 hr’ one. Indeed, the ‘0.5 hr’ network still satisfies all the predictions of BQS and strongly resembles the ‘0 hr’ network (Figure 9A,B,G). In contrast, at 1 and 2 hr after the stimulus, a marked deviation from BQS is observed. A significant number of new long loops are created, peaking at 1 hr and declining slightly by 2 hr (Figure 9C,E). 22 long feedback loops remain at 2 hr, but interestingly all depend on the transcriptional interaction between RUNX1 and CEBPB. The probability of creating additional long feedback loops is noticeably larger at 1 and 2 hr than in the previous networks (Figure 9G). There is also a significant increase in the number of 4-node unbuffered motifs at 1 hr, though this does not persist in the ‘2 hr’ GRN. However, some components of BQS remain unchanged in the stimulus response. Incomplete feedback loops still remain preferentially short (Figure 9—figure supplement 1A,E,I), TF cross regulation remains essentially unchanged (Figure 9—figure supplement 1D,H,L) and the numbers of unbuffered 3-node motifs (Figure 9—figure supplement 1B,F,J) and unregulated TFs (Figure 9—figure supplement 1C,G,K) remain low. Taken together, these observations show that in response to a stimulus that changes the transcriptional profile, there is a modest and probably transient loss of BQS as the GRN moves into a new configuration.10.7554/eLife.02863.035Figure 9.BQS during a transcriptional program activation in dendritic cells.
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom email@example.com.