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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >UNDERSTANDING DISTAL TRANSCRIPTIONAL REGULATION FROM SEQUENCE, EXPRESSION AND INTERACTOME PERSPECTIVES
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UNDERSTANDING DISTAL TRANSCRIPTIONAL REGULATION FROM SEQUENCE, EXPRESSION AND INTERACTOME PERSPECTIVES

机译：从序列，表达和交互角度看待远距离转录调控

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Gene regulation in eukaryotes involves a complex interplay between the proximal promoternand distal genomic elements (such as enhancers) which work in concert to drivenprecise spatio-temporal gene expression. The experimental localization and characterizationnof gene regulatory elements is a very complex and resource-intensive process. Thencomputational identification of regulatory regions that confer spatiotemporally specificntissue-restricted expression of a gene is thus an important challenge for computationalnbiology. One of the most popular strategies for enhancer localization from DNA sequencenis the use of conservation-based prefiltering and more recently, the use of canonical (transcriptionnfactor motifs) or de novo tissue-specific sequence motifs. However, there is annongoing effort in the computational biology community to further improve the fidelity ofnenhancer predictions from sequence data by integrating other, complementary genomicnmodalities.nIn this work, we propose a framework that complements existing methodologies fornprospective enhancer identification. The methods in this work are derived from twonkey insights: (i) that chromatin modification signatures can discriminate proximal andndistally located regulatory regions and (ii) the notion of promoter-enhancer cross-talkn∗Corresponding author.n219n220 A. Rao et al.n(as assayed in 3C/5C experiments) might have implications in the search for regulatorynsequences that co-operate with the promoter to yield tissue-restricted, gene-specificnexpression.
机译：真核生物中的基因调控涉及近端启动子和远端基因组元件（例如增强子）之间的复杂相互作用，这些相互作用共同作用以驱动精确的时空基因表达。基因调控元件的实验定位和表征是一个非常复杂且资源密集的过程。因此，计算鉴定赋予基因时空特异性组织限制表达的调控区，对于计算生物学是一个重要的挑战。用于从DNA序列进行增强子定位的最流行策略之一是使用基于保守的预过滤，最近，使用规范（转录因子基序）或从头组织特异性序列基序。但是，计算生物学界正在进行不懈的努力，以通过整合其他互补的基因组模式进一步提高序列数据对增强子预测的保真度。[n]在这项工作中，我们提出了一个框架，该框架可补充现有的用于预期的增强子鉴定的方法。这项工作中的方法来自两个重要的见解：（i）染色质修饰签名可以区分位于近端和近端的调节区，以及（ii）启动子与增强子串扰的概念。通讯作者。n219n220A. Rao等。 （如在3C / 5C实验中测定的）（可能与寻找与启动子协同产生组织限制性基因特异性表达的调控序列有关）。

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