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
Related in: MedlinePlus
Mentions: Some TFs, however, must be regulated by other TFs in order for the GRN to be able to combine information from multiple pathways and change state depending on different circumstances. In order to satisfy BQS, highly connected TFs should either be regulated by a large number of other TFs or should themselves regulate a large number of target TFs, but not both (since otherwise the TF in question is significantly more susceptible to becoming part of a 3-gene feedback loop after addition of a link); in other words, highly centralised control is disallowed. This prediction of BQS is indeed verified in E. coli (Figure 4B), S. cerevisiae (Figure 4—figure supplement 3A) and human (Figure 4—figure supplement 3B). The E. coli TF with the largest number of ‘outgoing regulatory connections’ regulates 38 other TF genes, but is itself regulated by only one TF; the TF with the largest number of ‘incoming regulatory connections’ is regulated by nine other TFs but itself regulates only one TF gene. There are no E. coli TFs that are both highly regulated and highly regulating (in fact, there are no TFs regulating >2 other TFs that are themselves regulated by >2 TFs).
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom email@example.com.