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bioRxiv · 10.64898/2026.06.01.729264

A comparative analysis of promoter-proximal pausing reveals kinetic and distributional dimensions of variation

Zeng, X.·Barshad, G.·Hassett, R.·Rice, E. J.·Danko, C. G.·Siepel, A.·Zhao, Y.
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Abstract

Promoter-proximal pausing of RNA polymerase II is a key regulatory checkpoint in metazoan transcription. Despite extensive study of this process, quantitative methods for comparing pausing dynamics across biological contexts have been lacking. Here we introduce a model-based framework for rigorous comparative analysis of both pause-escape kinetics and pause-site distributions. We apply this framework to public datasets together with newly generated PRO-seq and Micro-C data from primate immune cells, enabling a broad comparison of promoter-proximal pausing across conditions, cell types, and species. Analyses of these datasets revealed striking differences across transcriptional perturbations and distinct patterns of variation in pause-escape kinetics and pause-site distributions across cell types and species, with only weak coupling between them. Integration with chromatin and sequence features showed that lower pause-escape rates are associated with stronger promoter-proximal nucleosome occupancy, whereas changes in pause-site dispersion are associated with sequence features such as GC skew. Together, these results reveal kinetic and distributional dimensions of pausing variation across biological contexts.

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Zeng, X., Barshad, G., Hassett, R., Rice, E. J., Danko, C. G., Siepel, A., Zhao, Y.. 2026-06-04. A comparative analysis of promoter-proximal pausing reveals kinetic and distributional dimensions of variation. https://doi.org/10.64898/2026.06.01.729264

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