Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model

Gene transcription often occurs in discrete bursts, and it can be difficult to deduce the underlying regulatory mechanisms for transcriptional bursting with limited experimental data. Here, we categorize numerous states of single eukaryotic genes and identify 6 essential transcriptional events, each...

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Main Authors: Renjie Wu, Bangyan Zhou, Wei Wang, Feng Liu
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2023-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0253
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author Renjie Wu
Bangyan Zhou
Wei Wang
Feng Liu
author_facet Renjie Wu
Bangyan Zhou
Wei Wang
Feng Liu
author_sort Renjie Wu
collection DOAJ
description Gene transcription often occurs in discrete bursts, and it can be difficult to deduce the underlying regulatory mechanisms for transcriptional bursting with limited experimental data. Here, we categorize numerous states of single eukaryotic genes and identify 6 essential transcriptional events, each comprising a series of state transitions; transcriptional bursting is characterized as a sequence of 4 events, capable of being organized in various configurations, in addition to the beginning and ending events. By associating transcriptional kinetics with mean durations and recurrence probabilities of the events, we unravel how transcriptional bursting is modulated by various regulators including transcription factors. Through analytical derivation and numerical simulation, this study reveals key state transitions contributing to transcriptional sensitivity and specificity, typical characteristics of burst profiles, global constraints on intrinsic transcriptional noise, major regulatory modes in individual genes and across the genome, and requirements for fast gene induction upon stimulation. It is illustrated how biochemical reactions on different time scales are modulated to separately shape the durations and ordering of the events. Our results suggest that transcriptional patterns are essentially controlled by a shared set of transcriptional events occurring under specific promoter architectures and regulatory modes, the number of which is actually limited.
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spelling doaj.art-e0fdcf15ebcc4b23b49f2a608446da662024-04-03T09:53:24ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742023-01-01610.34133/research.0253Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based ModelRenjie Wu0Bangyan Zhou1Wei Wang2Feng Liu3National Laboratory of Solid State Microstructures, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China.National Laboratory of Solid State Microstructures, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China.National Laboratory of Solid State Microstructures, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China.National Laboratory of Solid State Microstructures, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China.Gene transcription often occurs in discrete bursts, and it can be difficult to deduce the underlying regulatory mechanisms for transcriptional bursting with limited experimental data. Here, we categorize numerous states of single eukaryotic genes and identify 6 essential transcriptional events, each comprising a series of state transitions; transcriptional bursting is characterized as a sequence of 4 events, capable of being organized in various configurations, in addition to the beginning and ending events. By associating transcriptional kinetics with mean durations and recurrence probabilities of the events, we unravel how transcriptional bursting is modulated by various regulators including transcription factors. Through analytical derivation and numerical simulation, this study reveals key state transitions contributing to transcriptional sensitivity and specificity, typical characteristics of burst profiles, global constraints on intrinsic transcriptional noise, major regulatory modes in individual genes and across the genome, and requirements for fast gene induction upon stimulation. It is illustrated how biochemical reactions on different time scales are modulated to separately shape the durations and ordering of the events. Our results suggest that transcriptional patterns are essentially controlled by a shared set of transcriptional events occurring under specific promoter architectures and regulatory modes, the number of which is actually limited.https://spj.science.org/doi/10.34133/research.0253
spellingShingle Renjie Wu
Bangyan Zhou
Wei Wang
Feng Liu
Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model
Research
title Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model
title_full Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model
title_fullStr Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model
title_full_unstemmed Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model
title_short Regulatory Mechanisms for Transcriptional Bursting Revealed by an Event-Based Model
title_sort regulatory mechanisms for transcriptional bursting revealed by an event based model
url https://spj.science.org/doi/10.34133/research.0253
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AT fengliu regulatorymechanismsfortranscriptionalburstingrevealedbyaneventbasedmodel