Asymmetry between Activation and Deactivation during a Transcriptional Pulse.
Asymmetry between Activation and Deactivation during a Transcriptional Pulse.
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DOI：
10.1016/j.cels.2017.10.013
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发表时间：
2017-12-27
期刊：
影响因子：
9.3
通讯作者：
Davis JRE
中科院分区：
文献类型：
--
作者：
Dunham LSS;Momiji H;Harper CV;Downton PJ;Hey K;McNamara A;Featherstone K;Spiller DG;Rand DA;Finkenstädt B;White MRH;Davis JRE
真核细胞中的转录发生在基因特异性爆发或活性脉冲中。最近的研究确定了一系列转录活性的“开启状态”，穿插着不活动的时期，但这些“关闭状态”和转录失活的过程知之甚少。为了研究在失活过程中发生了什么，我们研究了可变速率之间切换的动态。我们测量了活的单细胞表达的荧光素酶报告人生长激素或人催乳素启动子在垂体细胞系。随后，我们应用了统计可变速率模型的转录，单分子FISH验证，估计转录速率之间的切换。假设转录可以在任何时候切换到任何速率，我们发现，转录激活主要发生作为一个单一的开关，而失活发生分级，逐步降低转录速率。用毛喉素或组蛋白去乙酰化酶抑制剂进行染色质重塑来实验性改变cAMP信号传导，可以改变定义的转录状态的持续时间。我们的研究结果揭示了转录激活和失活机制独立，不对称的过程。基因转录在可变速率之间切换单细胞显微镜和数学建模量化开关动力学我们观察到转录突发激活/失活的不对称性Dunham et al.将数学工具应用于单细胞成像数据，以量化基因表达动态，揭示转录突发调控中的全有或全无激活和分级失活模式。
Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active “on-states,” interspersed with periods of inactivity, but these “off-states” and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line. Subsequently, we applied a statistical variable-rate model of transcription, validated by single-molecule FISH, to estimate switching between transcriptional rates. Under the assumption that transcription can switch to any rate at any time, we found that transcriptional activation occurs predominantly as a single switch, whereas deactivation occurs with graded, stepwise decreases in transcription rate. Experimentally altering cAMP signalling with forskolin or chromatin remodelling with histone deacetylase inhibitor modifies the duration of defined transcriptional states. Our findings reveal transcriptional activation and deactivation as mechanistically independent, asymmetrical processes. Gene transcription switches between variable rates Single-cell microscopy and mathematical modeling quantifies switch dynamics We observe an asymmetry in the activation/deactivation of transcriptional bursts Dunham et al. apply mathematical tools to single-cell imaging data to quantify gene expression dynamics, revealing a pattern of all-or-nothing activation and a graded deactivation in the regulation of transcriptional bursts.
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在单细胞水平上表观遗传调节的动力学。
DOI：
10.1126/science.aab2956
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bintu L;Yong J;Antebi YE;McCue K;Kazuki Y;Uno N;Oshimura M;Elowitz MB
通讯作者：
Elowitz MB
影响因子：
30.8
作者：
Hammar P;Walldén M;Fange D;Persson F;Baltekin O;Ullman G;Leroy P;Elf J
通讯作者：
Elf J
影响因子：
9.2
作者：
Corrigan, Adam M.;Chubb, Jonathan R.
通讯作者：
Chubb, Jonathan R.
影响因子：
30.8
作者：
Becskei, A;Kaufmann, BB;van Oudenaarden, A
通讯作者：
van Oudenaarden, A
影响因子：
4
作者：
Harper, Claire V.;Featherstone, Karen;White, Michael R. H.
通讯作者：
White, Michael R. H.