DNA Target Search in Chromatin Compartments under Stochastic Resetting

Abstract

The search kinetics of specific DNA targets by transcription factors (TF) in eukaryotic cells is a complex process modulated by the structure of the chromatin, topologically associated domains, chromatin compartments, and the intracellular environment. In this work, we study the search for the target within the chromatin compartments under stochastic resetting of the TF to the transcription condensates. We show that intersegmental jumps and resetting can have dual effects by enhancing and reducing search efficiency depending on the resetting position of the TF. Intersegmental jumps can facilitate escape from chromatin compartments and increase search times by trapping the searcher. We further show that the size of the compartment critically influences the search dynamics and can help optimize search time. Resetting can improve search efficiency only when it occurs near the target site. In addition, resetting to a broad region rather than a point can further reduce search time. We also investigate the cost associated with resetting, which increases with resetting rate and decreases with intersegmental jump rate. Our analytical results, supported by numerical simulations, provide quantitative insights into the role of chromatin architecture and TF localization in regulating the search dynamics of TF.