Motifs enable communication efficiency and fault-tolerance in transcriptional networks

Abstract

AbstractAnalysis of the topology of transcriptional regulatory networks (TRNs) is an effective way to study the regulatory interactions between the transcription factors (TFs) and the target genes. TRNs are characterized by the abundance of motifs such as feed forward loops (FFLs), which contribute to their structural and functional properties. In this paper, we focus on the role of motifs (specifically, FFLs) in signal propagation in TRNs and the organization of the TRN topology with FFLs as building blocks. To this end, we classify nodes participating in FFLs (termed motif central nodes) into three distinct roles (namely, roles A, B and C), and contrast them with TRN nodes having high connectivity on the basis of their potential for information dissemination, using metrics such as network efficiency, path enumeration, epidemic models and standard graph centrality measures. We also present the notion of a three tier architecture and how it can help study the structural properties of TRN based on connectivity and clustering tendency of motif central nodes. Finally, we motivate the potential implication of the structural properties of motif centrality in design of efficient protocols of information routing in communication networks as well as their functional properties in global regulation and stress response to study specific disease conditions and identification of drug targets.