3 (')-5 (') crosstalk contributes to transcriptional bursting.
3 (')-5 (') crosstalk contributes to transcriptional bursting.
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3（'）-5（'）串扰有助于转录爆发。
DOI：
10.1186/s13059-020-02227-5
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发表时间：
2021-02-04
期刊：
影响因子：
12.3
通讯作者：
Hebenstreit D
中科院分区：
文献类型：
--
作者：
Cavallaro M;Walsh MD;Jones M;Teahan J;Tiberi S;Finkenstädt B;Hebenstreit D
哺乳动物细胞中的转录是一个复杂的随机过程，涉及聚合酶在基因和相分离的液体冷凝物之间的穿梭。它以爆发的方式发生，这导致同基因细胞群中mRNA种类的数量差异很大。已经确定了几个促成转录爆发的因素，通常被分类为内在的，换句话说，是单个基因的局部因素，或者是与细胞的宏观状态相关的外在因素。然而，一些可能的贡献者尚未被探索。在这里，我们专注于在3 ′和5 ′端的基因，使转录终止后重新启动的过程。使用贝叶斯方法，我们测量的诱导型转基因的转录爆发，显示聚合酶穿梭的扰动通常会减少突发大小，增加突发频率，从而限制转录噪音。基于配对末端标签测序（PolII ChIA-PET）的分析表明，这种效应是基因组范围内的。所观察到的噪声模式也再现了生成模型，该生成模型捕获了基因的末端和相分离的隔室之间的聚合酶通量的主要特征。基因3 ′端和5 ′端之间的相互作用促进聚合酶循环，是转录噪音的主要贡献者。在线版本包含补充材料，可在（10.1186/s13059-020-02227-5）获得。
Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to transcriptional bursting have been identified, usually classified as intrinsic, in other words local to single genes, or extrinsic, relating to the macroscopic state of the cell. However, some possible contributors have not been explored yet. Here, we focus on processes at the 3 ′ and 5 ′ ends of a gene that enable reinitiation of transcription upon termination. Using Bayesian methodology, we measure the transcriptional bursting in inducible transgenes, showing that perturbation of polymerase shuttling typically reduces burst size, increases burst frequency, and thus limits transcriptional noise. Analysis based on paired-end tag sequencing (PolII ChIA-PET) suggests that this effect is genome wide. The observed noise patterns are also reproduced by a generative model that captures major characteristics of the polymerase flux between the ends of a gene and a phase-separated compartment. Interactions between the 3 ′ and 5 ′ ends of a gene, which facilitate polymerase recycling, are major contributors to transcriptional noise. The online version contains supplementary material available at (10.1186/s13059-020-02227-5).
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
8.8
作者：
Bauer DLV;Tellier M;Martínez-Alonso M;Nojima T;Proudfoot NJ;Murphy S;Fodor E
通讯作者：
Fodor E
影响因子：
7.7
作者：
Cho, Won-Ki;Jayanth, Namrata;Cisse, Ibrahim I.
通讯作者：
Cisse, Ibrahim I.
影响因子：
1.9
作者：
BARTLETT, MS
通讯作者：
BARTLETT, MS
影响因子：
5.2
作者：
Bandiera L;Furini S;Giordano E
通讯作者：
Giordano E