Genome-wide inference reveals that feedback regulations constrain promoter-dependent transcriptional burst kinetics.

ABSTRACT: Gene expression in mammalian cells is highly variable and episodic, resulting in a series of discontinuous bursts of mRNAs. A challenge is to understand how static promoter architecture and dynamic feedback regulations dictate bursting on a genome-wide scale. Although single-cell RNA sequencing (scRNA-seq) provides an opportunity to address this challenge, effective analytical methods are scarce. We developed an interpretable and scalable inference framework, which combined experimental data with a mechanistic model to infer transcriptional burst kinetics (sizes and frequencies) and feedback regulations. Applying this framework to scRNA-seq data generated from embryonic mouse fibroblast cells, we found Simpson's paradoxes, i.e. genome-wide burst kinetics exhibit different characteristics i

SUBMITTER: Luo S 

PROVIDER: S-EPMC9874261 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature