Identifying regulatory elements in eukaryotic genomes
Identifying regulatory elements in eukaryotic genomes
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DOI：
10.1093/bfgp/elp014
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发表时间：
2009-07-01
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影响因子：
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通讯作者：
Ovcharenko, Ivan
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文献类型：
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作者：
Narlikar, Leelavati;Ovcharenko, Ivan
生物体的正常发育和功能取决于其所有基因在空间和时间上的精确表达。这些协调的表达模式主要通过转录调控过程来维持。转录调节由以组合方式结合DNA上的调节元件的蛋白质介导，其中转录因子结合位点的特定组合建立特定的调节密码。在这篇综述中，我们调查的实验和计算方法，面向识别复杂的真核生物基因组中的近端和远端基因调控元件。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，转录因子的协同性等，破译调控元件的遗传结构和功能的可用方法被突出显示。我们还讨论了在人类健康的背景下，通过在这些地区的一些突变的例子有严重的影响，在基因的失调，并与人类疾病密切相关的监管要素的相关性。
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.