Feed-forward loop network motif. Simulation of the feed forward motif acting as a filter of intrinsic noise in yeast (a) Network model of the feed forward motif. Gene X drives both genes Y and Z. Y also drives Z. X and Y cooperatively bind and activate Z. In these simulations (b, c), the input transcription factor (yellow) is held in a basal steady state of approximately 100 molecules. The stochastic input to the red gene (X) results in occasional spikes in transcription by this gene. The blue gene (Y), which is driven by the red gene's output, is also occasionally driven briefly to an active state, but its activity is delayed compared to the red gene. Consequently, the green gene, which can only be active when both its inputs are active at the same time, is never activated. In other words, the green gene has filtered out the noise in the yellow input transcription factor and the resulting spikes of activity seen in the red and blue genes. (b) Shows simulation results over an arbitrarily long period of time in order to highlight the frequency with which transcriptional noise spikes occur in the outputs of genes X and Y (but in gene Z). (c) Example of the same circuit simulated over a more realistic time window of 48 h shows the widths of the spikes produced by X and Y, and that Y output does not overlap significantly with X output. In consequence, the spikes in X and Y activity do not translate to a significant level of activity in Z.