A unified model for yeast transcript definition.
A unified model for yeast transcript definition.
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DOI：
10.1101/gr.164327.113
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发表时间：
2014-01
期刊：
影响因子：
7
通讯作者：
Hughes TR
中科院分区：
文献类型：
--
作者：
de Boer CG;van Bakel H;Tsui K;Li J;Morris QD;Nislow C;Greenblatt JF;Hughes TR
在基因组环境中识别基因是细胞解释基因组能力的核心。然而，总的来说，用来定义真核基因的信号描述得很差。在这里，我们推导出简单的分类器，使用酵母细胞可检测到的核酸序列特征来识别转录的起始和终止位置，并将其集成到一个统一模型(UM)中，该模型将转录作为一个整体进行建模。指示转录起始位置的顺式元件主要通过核小体耗尽发挥作用，使用合成的启动子系统，我们证明大多数这些元件足以在体内启动转录。Hrp1结合位点是终止子的主要特征；这些结合位点通常聚集在终止子区域，可以双向终止转录。UM通过使用隐马尔可夫模型对基因组的转录进行建模来预测全球转录结构，该模型的发射是起始和终止分类器的输出。我们用现有的RNA-SEQ数据验证了UM的新预测，并通过将模型预测的转录结构与随机设计的合成DNA片段的细胞生成的转录直接比较来进一步测试它。我们发现UM比单独的起始分类器更准确地识别转录起始点，这表明启动子和终止子元件的相对排列影响了它们的功能。我们的模型具体描述了细胞如何定义转录单位，解释了非基因转录本的存在，并提供了对基因组进化的洞察。
Identifying genes in the genomic context is central to a cell's ability to interpret the genome. Yet, in general, the signals used to define eukaryotic genes are poorly described. Here, we derived simple classifiers that identify where transcription will initiate and terminate using nucleic acid sequence features detectable by the yeast cell, which we integrate into a Unified Model (UM) that models transcription as a whole. The cis-elements that denote where transcription initiates function primarily through nucleosome depletion, and, using a synthetic promoter system, we show that most of these elements are sufficient to initiate transcription in vivo. Hrp1 binding sites are the major characteristic of terminators; these binding sites are often clustered in terminator regions and can terminate transcription bidirectionally. The UM predicts global transcript structure by modeling transcription of the genome using a hidden Markov model whose emissions are the outputs of the initiation and termination classifiers. We validated the novel predictions of the UM with available RNA-seq data and tested it further by directly comparing the transcript structure predicted by the model to the transcription generated by the cell for synthetic DNA segments of random design. We show that the UM identifies transcription start sites more accurately than the initiation classifier alone, indicating that the relative arrangement of promoter and terminator elements influences their function. Our model presents a concrete description of how the cell defines transcript units, explains the existence of nongenic transcripts, and provides insight into genome evolution.
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影响因子：
64.8
作者：
Brogaard, Kristin;Xi, Liqun;Wang, Ji-Ping;Widom, Jonathan
通讯作者：
Widom, Jonathan
影响因子：
16
作者：
Badis, Gwenael;Chan, Esther T.;van Bakel, Harm;Pena-Castillo, Lourdes;Tillo, Desiree;Tsui, Kyle;Carlson, Clayton D.;Gossett, Andrea J.;Hasinoff, Michael J.;Warren, Christopher L.;Gebbia, Marinella;Talukder, Shaheynoor;Yang, Ally;Mnaimneh, Sanie;Terterov, Dimitri;Coburn, David;Yeo, Ai Li;Yeo, Zhen Xuan;Clarke, Neil D.;Lieb, Jason D.;Ansari, Aseem Z.;Nislow, Corey;Hughes, Timothy R.
通讯作者：
Hughes, Timothy R.
影响因子：
10.5
作者：
Barabino, SML;Hubner, W;Keller, W
通讯作者：
Keller, W
影响因子：
11.4
作者：
Dichtl, B;Blank, D;Keller, W
通讯作者：
Keller, W
影响因子：
64.5
作者：
Basehoar, AD;Zanton, SJ;Pugh, BF
通讯作者：
Pugh, BF