Khan Mohsin A F, Soto-Jimenez Luz Mayela, Howe Timothy, Streit Andrea, Sosinsky Alona, Stern Claudio D
Department of Cell & Developmental Biology, University College London, London, United Kingdom.
Genesis. 2013 May;51(5):311-24. doi: 10.1002/dvg.22375. Epub 2013 Mar 30.
The discovery of cis-regulatory elements is a challenging problem in bioinformatics, owing to distal locations and context-specific roles of these elements in controlling gene regulation. Here we review the current bioinformatics methodologies and resources available for systematic discovery of cis-acting regulatory elements and conserved transcription factor binding sites in the chick genome. In addition, we propose and make available, a novel workflow using computational tools that integrate CTCF analysis to predict putative insulator elements, enhancer prediction, and TFBS analysis. To demonstrate the usefulness of this computational workflow, we then use it to analyze the locus of the gene Sox2 whose developmental expression is known to be controlled by a complex array of cis-acting regulatory elements. The workflow accurately predicts most of the experimentally verified elements along with some that have not yet been discovered. A web version of the CTCF tool, together with instructions for using the workflow can be accessed from http://toolshed.g2.bx.psu.edu/view/mkhan1980/ctcf_analysis. For local installation of the tool, relevant Perl scripts and instructions are provided in the directory named "code" in the supplementary materials.
由于顺式调控元件在控制基因调控中的远端位置和上下文特异性作用,其发现是生物信息学中的一个具有挑战性的问题。在这里,我们综述了当前可用于系统发现鸡基因组中顺式作用调控元件和保守转录因子结合位点的生物信息学方法和资源。此外,我们提出并提供了一种新颖的工作流程,该流程使用计算工具整合CTCF分析以预测假定的绝缘子元件、增强子预测和TFBS分析。为了证明这种计算工作流程的实用性,我们随后用它来分析基因Sox2的基因座,已知其发育表达受一系列复杂的顺式作用调控元件控制。该工作流程准确地预测了大多数经实验验证的元件以及一些尚未发现的元件。CTCF工具的网络版本以及使用该工作流程的说明可从http://toolshed.g2.bx.psu.edu/view/mkhan1980/ctcf_analysis获取。对于该工具的本地安装,补充材料中名为“代码”的目录中提供了相关的Perl脚本和说明。