Narlikar Leelavati, Ovcharenko Ivan
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Brief Funct Genomic Proteomic. 2009 Jul;8(4):215-30. doi: 10.1093/bfgp/elp014. Epub 2009 Jun 4.
Proper development and functioning of an organism depends on precise spatial and temporal expression of all its genes. These coordinated expression-patterns are maintained primarily through the process of transcriptional regulation. Transcriptional regulation is mediated by proteins binding to regulatory elements on the DNA in a combinatorial manner, where particular combinations of transcription factor binding sites establish specific regulatory codes. In this review, we survey experimental and computational approaches geared towards the identification of proximal and distal gene regulatory elements in the genomes of complex eukaryotes. Available approaches that decipher the genetic structure and function of regulatory elements by exploiting various sources of information like gene expression data, chromatin structure, DNA-binding specificities of transcription factors, cooperativity of transcription factors, etc. are highlighted. We also discuss the relevance of regulatory elements in the context of human health through examples of mutations in some of these regions having serious implications in misregulation of genes and being strongly associated with human disorders.
生物体的正常发育和功能依赖于其所有基因精确的时空表达。这些协调的表达模式主要通过转录调控过程得以维持。转录调控由蛋白质以组合方式与DNA上的调控元件结合介导，其中转录因子结合位点的特定组合建立了特定的调控密码。在本综述中，我们概述了旨在识别复杂真核生物基因组中近端和远端基因调控元件的实验和计算方法。重点介绍了通过利用各种信息来源（如基因表达数据、染色质结构、转录因子的DNA结合特异性、转录因子的协同作用等）来解读调控元件的遗传结构和功能的现有方法。我们还通过一些区域发生的突变的例子，讨论了调控元件在人类健康背景下的相关性，这些突变对基因调控异常有严重影响，并与人类疾病密切相关。
