Promoter-mediated Transcriptional Dynamics
Promoter-mediated Transcriptional Dynamics
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启动子介导的转录动力学
DOI：
10.1016/j.bpj.2013.12.011
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发表时间：
2014-01-21
影响因子：
3.4
通讯作者：
Zhou, Tianshou
中科院分区：
文献类型：
--
作者：
Zhang, Jiajun;Zhou, Tianshou
真核细胞中的基因通常由包含多种转录因子的多个结合位点的复杂启动子调控，但启动子动力学如何影响转录动力学仍然知之甚少。在本研究中，我们分析了转录调控水平上的基因模型，其中包括启动子结构（PS）的复杂性，即转录出口（即启动子的ON状态）和转换模式（由启动子活性状态之间的转换率组成的矩阵描述）。我们发现转录的多个出口是产生mRNA多模态分布的重要来源，但具有相同转换模式的启动子可以导致不同模式的多模态，这取决于转录因子的调节。反过来，对于模型中相似的mRNA分布，平均开或关时间分布可能表现出不同的特征，从而提供关于PS的补充信息。此外，我们证明转录噪声可以用平均开和关时间的非线性函数来表征。这些结果不仅揭示了启动子介导的转录动力学的基本特征，而且为基于转录输出特征推断PS提供了有用的特征。
Genes in eukaryotic cells are typically regulated by complex promoters containing multiple binding sites for a variety of transcription factors, but how promoter dynamics affect transcriptional dynamics has remained poorly understood. In this study, we analyze gene models at the transcriptional regulation level, which incorporate the complexity of promoter structure (PS) defined as transcriptional exits (i.e., ON states of the promoter) and the transition pattern (described by a matrix consisting of transition rates among promoter activity states). We show that multiple exits of transcription are the essential origin of generating multimodal distributions of mRNA, but promoters with the same transition pattern can lead to multimodality of different modes, depending on the regulation of transcriptional factors. In turn, for similar mRNA distributions in the models, the mean ON or OFF time distributions may exhibit different characteristics, thus providing the supplemental information on PS. In addition, we demonstrate that the transcriptional noise can be characterized by a nonlinear function of mean ON and OFF times. These results not only reveal essential characteristics of promoter-mediated transcriptional dynamics but also provide signatures useful for inferring PS based on characteristics of transcriptional outputs.