Slow nucleosome dynamics set the transcriptional speed limit and induce RNA polymerase II traffic jams and bursts

Nucleosomes are recognized as key regulators of transcription. However, the relationship between slow nucleosome unwrapping dynamics and bulk transcriptional properties has not been thoroughly explored. Here, an agent-based model that we call the dynamic defect Totally Asymmetric Simple Exclusion Process (ddTASEP) was constructed to investigate the effects of nucleosome-induced pausing on transcriptional dynamics. Pausing due to slow nucleosome dynamics induced RNAPII convoy formation, which would cooperatively prevent nucleosome rebinding leading to bursts of transcription. The mean first passage time (MFPT) and the variance of first passage time (VFPT) were analytically expressed in terms of the nucleosome rate constants, allowing for the direct quantification of the effects of nucleosome-induced pausing on pioneering polymerase dynamics. The mean first passage elongation rate gamma(h(c), h(o)) is inversely proportional to the MFPT and can be considered to be a new axis of the ddTASEP phase diagram, orthogonal to the classical alpha beta-plane (where alpha and beta are the initiation and termination rates). Subsequently, we showed that, for beta = 1, there is a novel jamming transition in the alpha gamma-plane that separates the ddTASEP dynamics into initiation-limited and nucleosome pausing-limited regions. We propose analytical estimates for the RNAPII density rho, average elongation rate v, and transcription flux J and verified them numerically. We demonstrate that the intra-burst RNAPII waiting times t(in) follow the time-headway distribution of a max flux TASEP and that the average interburst interval (t(IBI)) over bar correlates with the index of dispersion De- . In the limit gamma -> 0, the average burst size reaches a maximum set by the closing rate h(c). When alpha << 1, the burst sizes are geometrically distributed, allowing large bursts even while the average burst size (N-B) over bar is small. Last, preliminary results on the relative effects of static and dynamic defects are presented to show that dynamic defects can induce equal or greater pausing than static bottle necks.

Automated summary

This study investigates the effects of nucleosome-induced pausing on transcriptional dynamics by constructing an agent-based model. The results show that slow nucleosome unwrapping dynamics can induce the formation of RNAPII convoys, preventing nucleosome rebinding and leading to bursts of transcription.