南京大学学报(自然科学版) ›› 2020, Vol. 56 ›› Issue (3): 418–429.doi: 10.13232/j.cnki.jnju.2020.03.010

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基因转录爆发的建模研究

李佳云,吴人杰()   

  1. 南京大学物理学院，南京，210093
  • 收稿日期:2020-05-14 出版日期:2020-05-30 发布日期:2020-06-03
  • 通讯作者: 吴人杰 E-mail:15995920872@163.com
  • 基金资助:
    国家自然科学基金(11874209)

Modeling of transcriptional bursting

Jiayun Li,Renjie Wu()   

  1. School of Physics，Nanjing University，Nanjing，210093，China
  • Received:2020-05-14 Online:2020-05-30 Published:2020-06-03
  • Contact: Renjie Wu E-mail:15995920872@163.com

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摘要：

基因转录是细胞最重要的活动之一，涉及众多分子事件，且不同基因间存在显著差异性.建立基因转录的模型有助于理解复杂的转录动力学和调控机制.如何构建合适的转录模型依然具有大的挑战性.近年来的实验发现，转录爆发是一类普遍的转录模式，揭示其特征（如转录爆发的频率和大小以及激活态和沉默态的持续时间等）和调控机制是当前的研究热点.人们相继提出两态模型和多态模型来理解转录现象.有些模型不再是简单的唯象模型，而是考虑了转录的分子过程，能够深入研究转录的内在机理.结合最近的实验和理论研究，综述不同转录模型的特点、合理性及其适用范围，特别比较了各个模型的优缺点，有助于在研究中选取合适的转录模型.随着单细胞实验技术的发展，构建基因转录的定量模型将起到越来越重要的作用.

关键词: 基因转录, 转录爆发, 两态模型, 多态模型, 适用范围

Abstract:

Gene transcription is one of the most important cellular activities，involving various molecular events and exhibiting great variability among genes. Modeling of gene transcription can promote our understanding of the complex mechanisms for transcriptional kinetics and regulation. It is still challenging to construct suitable models under different conditions. It is established that transcriptional bursting has been a ubiquitous mode; it is essential to unravel the features of transcriptional bursting (such as burst frequency and size，as well as the duration of active and inactive gene states) and underlying regulatory mechanisms. Two?state and multi?state models have been proposed to investigate transcriptional bursting. Some models are no longer simple phenomenological ones; instead，they take into account molecular events involved in transcription and thus can be used to explore the intrinsic mechanisms for transcription. Integrating recent experimental and theoretical studies，the current work reviews widely used models of transcriptional bursting in the literature，including the two?state，continuum，multi?scale，and Wang?Liu?Wang (WLW) models. We analyze the essential features，rationality and applicability of models. Specifically，we list the advantages and disadvantages of these models to facilitate choosing an appropriate model in a special situation. With the advancement of single?cell technology，building quantitative models of gene transcription will play an increasingly important role.

Key words: gene transcription, transcriptional bursting, two?state model, multi?state model, scope of application

中图分类号: 

  • Q615

图 1

单细胞中的转录爆发"

图2

转录爆发的典型特征"

图3

转录模型"

表1

转录模型的适用性"

模型

单态模型

（图3a）

两态模型

（图3b）

多态模型（图3c至图3i）

多ON模型

（含连续性模型）

多OFF模型

（含棘轮模型和多尺度模型）

WLW模型
激活态的持续时间分布/图2a主要时图2a，少部分情况下为峰值不为0的单峰分布，但是也接近图2a图2a主要时图2a，少部分情况下为峰值不为0的单峰分布，但是也接近图2a
沉默态的持续时间分布/图2c图2c图2b，图2c图2b，图2c
mRNA数量分布图2e图2d至图2f图2d至图2g图2d至图2g图2d至图2g

保

留

信

息

细胞群体水平的平均mRNA信息
mRNA的噪声强度、爆发频率和大小、激活态和沉默态的平均持续时间
mRNA分布性质
激活态持续时间分布沉默态持续时间分布

激活态和沉默态的

持续时间分布

精确度低中等较高较高高
参数很少，可由实验测得少，可由实验测得中等，部分可由实验测得，部分需要假设且要与实验相符中等，部分可由实验测得，部分需要假设且要与实验相符多，主要步骤可由实验测得，部分未明确的机制需要假设
计算量很小小中等中等大
适用情况mRNA或蛋白质的CV较小，不考虑单细胞中mRNA的时变研究单细胞转录产物数量变化，基因状态切换以及转录调控等mRNA数量呈多峰分布、激活态时长呈单峰分布，或者研究转录调控和信号传导时采用多ON态模型 。在研究相分离对转录的影响时可用连续性模型，侧重于转录因子或者聚合酶的局部时空变化对转录的影响研究周期性和能耗时，可采用棘轮模型。研究温度、启动子序列、转录因子等对转录的影响时用多尺度，侧重于脚手架结构对转录的影响研究转录因子自身生物功能对转录过程的影响
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