Figure 3

Topological organization of signal integration. (A) Decomposition of the TR network by removing its top- (input TFs) and bottom layers (output nodes) identifies the intermediate TF layer, which, based on the high local density and distribution of connections, is naturally subdivided into three major groups (organizers), as well as a number of isolated TFs. The connections between organizers are sparse. Nodes are arranged hierarchically based on the direction of information flow. The chain of links colored red shows the longest path through the network. Regulatory signals flow from darker nodes towards lighter ones. (B) The three emerging organizers of the yeast TR network are enclosed by blue, red, and green rectangles, respectively, while isolated intermediate TFs are on the right. The relative size and color code of each node conform to the descriptions given in Fig. 2B. Within organizers the density of links is more than 10 times higher than that between the organizers. Input TF nodes regulating the intermediate TFs in the organizers are shown by rectangles. The blue nodes on the left side of O1, the green ones on the right of O3, and the red ones above/below O2 are the inputs that regulate each one organizer. The magenta, cyan and yellow nodes regulate pairs of organizers, as indicated by the links. Note that there is no input TF regulating all the three organizers. The number of transcriptional inputs for each of the intermediate TFs is shown in parentheses. Essential TFs (+) and those with autoregulatory loops (@) are indicated. (C) Transcriptional response of organizers to hyperosmotic shock. The double Z scores (ordinate) [13] measure the significance of the response of each organizer node plus its target genes to the external condition as compared to the control condition (a strong up- and downregulation both give a high Z score). The numbers in the bottom part of each graph denote the average double Z scores for O1 (blue) O2 (red) and O3 (green), respectively, while the colored dots represent the average double Z-score of genes regulated by the indicated intermediate TF. Black dots represent the same for the input TF(s) directly regulating the indicated intermediate TF.