Identifying pattern-defined regulatory islands in mammalian genomes.
Identifying pattern-defined regulatory islands in mammalian genomes.
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识别哺乳动物基因组中模式定义的调控岛。
DOI：
10.1073/pnas.0704028104
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发表时间：
2007
影响因子：
11.1
通讯作者：
Liu,Xuedong
中科院分区：
文献类型：
--
作者：
Cheung,TomH;Barthel,KristenKB;Kwan,YinLam;Liu,Xuedong
识别哺乳动物基因组中的顺式调控区域是理解转录调控的关键挑战。然而，由于对这些调控元件在基因组中的组织和位置的了解有限，这些控制差异基因表达的调控元件的识别和功能表征受到了阻碍。我们假设跨物种保守的基因也将在其转录调控水平上表现出保守性，并且这将反映在介导这种调控的顺式元件的组织中。使用计算方法，鉴定出在人类、大鼠和小鼠基因组中顺序和间隔绝对保守的转录因子结合位点簇。我们将这些区域称为模式定义的监管岛（PRI）。我们发现这些序列通常是转录调控的活性位点。这些 PRI 出现在搜索所涵盖的 5 亿个碱基对中约 1.1%，并且主要位于基因组的非编码区域。我们表明，PRI 的前提可用于识别先前已知的和新的顺式调节区域，控制受肌原性分化调节的基因。因此，PRI 可能代表哺乳动物基因组中顺式调控元件结构的基本特性，并且可以利用该特征来精确定位控制细胞类型特异性基因表达的关键转录调控元件。
Identifying cis-regulatory regions in mammalian genomes is a key challenge toward understanding transcriptional regulation. However, identification and functional characterization of those regulatory elements governing differential gene expression has been hampered by the limited understanding of their organization and locations in genomes. We hypothesized that genes that are conserved across species will also display conservation at the level of their transcriptional regulation and that this will be reflected in the organization of cis-elements mediating this regulation. Using a computational approach, clusters of transcription factor binding sites that are absolutely conserved in order and in spacing across human, rat, and mouse genomes were identified. We term these regions pattern-defined regulatory islands (PRIs). We discovered that these sequences are frequently active sites of transcriptional regulation. These PRIs occur in ≈1.1% of the half-billion base pairs covered in the search and are located mainly in noncoding regions of the genome. We show that the premise of PRIs can be used to identify previously known and novel cis-regulatory regions controlling genes regulated by myogenic differentiation. Thus, PRIs may represent a fundamental property of the architecture of cis-regulatory elements in mammalian genomes, and this feature can be exploited to pinpoint critical transcriptional regulatory elements governing cell type-specific gene expression.