Analysis of Genomic Sequence Motifs for Deciphering Transcription Factor Binding and Transcriptional Regulation in Eukaryotic Cells.
Analysis of Genomic Sequence Motifs for Deciphering Transcription Factor Binding and Transcriptional Regulation in Eukaryotic Cells.
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DOI：
10.3389/fgene.2016.00024
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发表时间：
2016
影响因子：
3.7
通讯作者：
Boeva V
中科院分区：
文献类型：
--
作者：
Boeva V
真核生物基因组包含多种结构模式：重复元件、DNA和RNA相关蛋白的结合位点、剪接位点等。通常，这些结构化模式可以形式化为基元，并使用适当的数学模型（如位置权重矩阵和IUPAC共识）进行描述。在基因组序列分析的背景下，通常对基序进行两个关键任务。这些是：从特定的基序数据库中识别一组过度代表性的基序的DNA区域，以及重新发现过度代表性的基序。在这里，我们描述现有的方法来执行这两个任务的基序特征转录因子结合。当应用于ChIP-seq和ChIP-exo实验的输出，或共调节基因的启动子区域时，基序分析技术允许预测转录因子结合事件，并能够识别转录调节因子和共调节因子。基序分析的有用性在本综述中进一步举例说明了基序发现如何提高ChIP-seq和ChIP-exo实验中的峰值调用，并且当与基因表达信息相结合时，可以深入了解转录调节的物理机制。
Eukaryotic genomes contain a variety of structured patterns: repetitive elements, binding sites of DNA and RNA associated proteins, splice sites, and so on. Often, these structured patterns can be formalized as motifs and described using a proper mathematical model such as position weight matrix and IUPAC consensus. Two key tasks are typically carried out for motifs in the context of the analysis of genomic sequences. These are: identification in a set of DNA regions of over-represented motifs from a particular motif database, and de novo discovery of over-represented motifs. Here we describe existing methodology to perform these two tasks for motifs characterizing transcription factor binding. When applied to the output of ChIP-seq and ChIP-exo experiments, or to promoter regions of co-modulated genes, motif analysis techniques allow for the prediction of transcription factor binding events and enable identification of transcriptional regulators and co-regulators. The usefulness of motif analysis is further exemplified in this review by how motif discovery improves peak calling in ChIP-seq and ChIP-exo experiments and, when coupled with information on gene expression, allows insights into physical mechanisms of transcriptional modulation.