Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Development. 2023 Jun 15;150(12). doi: 10.1242/dev.201546. Epub 2023 Jun 20.
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.
RNA 聚合酶对 DNA 的转录是一个不连续的过程,称为转录爆发。这种爆发行为在不同物种中都有观察到,并通过各种随机建模方法进行了量化。有大量证据表明,爆发是由转录机制主动调节的,并在调节发育过程中发挥作用。在转录的常用两态模型下,各种增强子、启动子和染色质微环境相关特征被发现对爆发事件的大小和频率产生不同的影响——这是两态模型的关键参数。建模和分析工具的进步表明,简单的两态模型和相关参数可能不足以描述这些特征之间的复杂关系。大多数实验和建模发现支持这样一种观点,即爆发是一种进化保守的转录控制特征,而不是转录过程中的意外副产品。随机转录模式有助于增强细胞适应性和执行适当的发育程序,这使得这种转录模式成为发育基因调控的一个重要特征。在这篇综述中,我们提出了转录爆发在发育中的作用的有力例证,并探讨了随机转录如何导致确定性的生物体发育这一问题。