Predicting Timescales of DNA Mediated Protein Assembly

Transcription initiation pioneers are proteins that are necessary to help remodel DNA into an exposed structure that supports gene transcription. For the GAGA pioneer factor, experiments have recently shown that its ability to form larger oligomers is impacted by DNA binding, with a direct impact on its residence times and recruitment of additional proteins needed for transcription. To study the collective dynamics and microscopic mechanisms that control this process, we need models that can capture the spatial and temporal dynamics of localization and assembly on and around DNA. Here we implemented a reaction-diffusion model to simulate proteins binding and forming higher-order complexes on chromatin. It allows dynamic tracking over a long timescale (milliseconds to seconds) with high spatial resolution and predicts how residence times on DNA are controlled by higher-order clustering of the pioneer proteins. We found that the binding rates between pioneers themselves as well as between protein and DNA are key parameters controlling their arrival times and lifetimes on DNA. Our results capture the distribution and diffusion of pioneer factors across the genome, with direct implications for how their dynamics impact productive transcription.