Fig. 1. Structure of eukaryotic regulatory networks. (A) The basic building blocks of regulatory networks are interactions between transcription factor proteins and cis-regulatory DNA sequences, protein–protein interactions affecting availability or activity of transcription factors, and hybridization of microRNAs to their targets. (B) Interactions among these factors form local regulatory motifs such as feed-forward loops, single input modules, multiple input modules, autoregulation, feed-back loops and regulator chains. In the diagrams, circles represent proteins, squares represent genes, and solid arrows represent regulatory interactions. Broken lines indicate protein production from a gene. (C) Regulatory pathways controlling biological processes (especially development) have hierarchical structure. Pathways controlling wing development in D. melanogaster at mid-embryonic (top), late embryonic (middle) and late larval (bottom) stages are reproduced from Abouheif and Wray (Abouheif and Wray, 2002). Reprinted with permission from AAAS. Layers of regulatory proteins interact before the ultimate activation of effector genes that give differentiated cells their characteristic properties. (D) Genes functioning in multiple pathways form an integrated genomic network. The transcriptional regulatory network for S. cerevisiae is shown here, modified from Babu et al. (Babu et al., 2004), with permission from Elsevier. (E) The genomic regulatory network for S. cerevisiae has a hierarchical structure similar to individual pathways. Image is modified from Yu and Gerstein (Yu and Gerstein, 2006, Proc. Natl. Acad. Sci. USA 103, 14724-14731), with permission. Copyright (2006) National Academy of Sciences, USA.