A Modeling Framework for Generation of Positional and Temporal Simulations of Transcriptional Regulation

We present a modeling framework aimed at capturing both the positional and temporal behavior of transcriptional regulatory proteins in eukaryotic cells. There is growing evidence that transcriptional regulation is the complex behavior that emerges not solely from the individual components, but rather from their collective behavior, including competition and cooperation. Our framework describes individual regulatory components using generic action oriented descriptions of their biochemical interactions with a DNA sequence. All the possible actions are based on the current state of factors bound to the DNA. We developed a rule builder to automatically generate the complete set of biochemical interaction rules for any given DNA sequence. Off-the-shelf stochastic simulation engines can model the behavior of a system of rules and the resulting changes in the configuration of bound factors can be visualized. We compared our model to experimental data at well-studied loci in yeast, confirming that our model captures both the positional and temporal behavior of transcriptional regulation.