ArticleNucleic acids research2023
Model-based characterization of the equilibrium dynamics of transcription initiation and promoter-proximal pausing in human cells.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Analysis of host and viral nascent and steady-state RNA levels in a human neuronal model of herpes simplex virus 1 infection.PLoS pathogens · 2026Article
- Transcription initiation drives dosage compensation establishment and maintenance in maleScience advances · 2026Article
- A comparative analysis of promoter-proximal pausing reveals kinetic and distributional dimensions of variation.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide dynamic nascent transcript profiles reveal that most paused RNA polymerases terminate.Nucleic acids research · 2026Article
- Base Composition Influences the Position and Precision of RNA Polymerase II Disassociation in Basal and Perturbed Conditions.bioRxiv : the preprint server for biology · 2025Article
- Article
- LIET model: capturing the kinetics of RNA polymerase from loading to termination.Nucleic acids research · 2025Article
- Probabilistic and machine-learning methods for predicting local rates of transcription elongation from nascent RNA sequencing data.Nucleic acids research · 2025Article
- Aberrant RNA polymerase initiation and processivity on the genome of a herpes simplex virus 1 mutant lacking ICP27.Journal of virology · 2024Article
- Transcriptional bursting dynamics in gene expression.Frontiers in genetics · 2024Review
- DNA-sequence and epigenomic determinants of local rates of transcription elongation.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In metazoans, both transcription initiation and the escape of RNA polymerase (RNAP) from promoter-proximal pausing are key rate-limiting steps in gene expression. These processes play out at physically proximal sites on the DNA template and appear to influence one another through steric interactions. Here, we examine the dynamics of these processes using a combination of statistical modeling, simulation, and analysis of real nascent RNA sequencing data. We develop a simple probabilistic model that jointly describes the kinetics of transcription initiation, pause-escape, and elongation, and the generation of nascent RNA sequencing read counts under steady-state conditions. We then extend this initial model to allow for variability across cells in promoter-proximal pause site locations and steric hindrance of transcription initiation from paused RNAPs. In an extensive series of simulations, we show that this model enables accurate estimation of initiation and pause-escape rates. Furthermore, we show by simulation and analysis of real data that pause-escape is often strongly rate-limiting and that steric hindrance can dramatically reduce initiation rates. Our modeling framework is applicable to a variety of inference problems, and our software for estimation and simulation is freely available.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.