Transcriptional bursting: stochasticity in deterministic development

Abstract

ABSTRACT The transcription of DNA by RNA polymerase occurs as a discontinuous process described as transcriptional bursting. This bursting behavior is observed across species and has been quantified using various stochastic modeling approaches. There is a large body of evidence that suggests the bursts are actively modulated by transcriptional machinery and play a role in regulating developmental processes. Under a commonly used two-state model of transcription, various enhancer-, promoter- and chromatin microenvironment-associated features are found to differentially influence the size and frequency of bursting events – key parameters of the two-state model. Advancement of modeling and analysis tools has revealed that the simple two-state model and associated parameters may not sufficiently characterize the complex relationship between these features. The majority of experimental and modeling findings support the view of bursting as an evolutionarily conserved transcriptional control feature rather than an unintended byproduct of the transcription process. Stochastic transcriptional patterns contribute to enhanced cellular fitness and execution of proper development programs, which posit this mode of transcription as an important feature in developmental gene regulation. In this Review, we present compelling examples of the role of transcriptional bursting in development and explore the question of how stochastic transcription leads to deterministic organism development.