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

Zeng, Xin, Barshad, Gilad, Hassett, Rebecca, Rice, Edward J, Danko, Charles G, Siepel, Adam, Zhao, Yixin (June 2026) A comparative analysis of promoter-proximal pausing reveals kinetic and distributional dimensions of variation. bioRxiv. ISSN 2692-8205 (Submitted)

PDF 10.64898.2026.06.01.729264.pdf - Submitted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (12MB)

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 across genes, cell types, and species. An application to available PRO-seq datasets revealed striking differences across perturbations, and comparative analyses across cell types and species highlighted distinct patterns of variation in both pause-escape kinetics and pause-site distributions, 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 establish a quantitative framework for comparative analysis of promoter-proximal pausing and reveal kinetic and distributional dimensions of pausing variation across biological contexts.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > quantitative biology bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression > promoter
CSHL Authors:	Siepel, Adam Zhao, Yixin Hassett, Rebecca Zeng, Xin
Communities:	CSHL labs > Siepel lab CSHL Post Doctoral Fellows
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	4 June 2026
Date Deposited:	25 Jun 2026 12:18
Last Modified:	25 Jun 2026 12:18
PMCID:	PMC13251929
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42229

Actions (login required)

Administrator's edit/view item