Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome
Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome
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DOI：
10.1073/pnas.231608898
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发表时间：
2002-01-22
影响因子：
11.1
通讯作者：
Eisen, MB
中科院分区：
文献类型：
--
作者：
Berman, BP;Nibu, Y;Eisen, MB
解释基因组序列的一个主要挑战是理解基因组如何编码指定基因将在何时何地表达的信息。这一过程的第一步是确定基因组中包含调控信息的区域。在高等真核生物中，这种顺式调节信息被组织成几百个碱基对的模块单元[顺式调节模块(CRM)]。这些顺式调节模块的一个共同特征是存在多个转录因子的多个结合位点。在这里，我们评估转录因子结合位点聚集的趋势可以作为计算识别顺式调节模块的基础的程度。通过利用已公布的在果蝇早期胚胎中活跃的五种转录因子的DNA结合特异性数据，我们确定了包含这些因子预测结合位点的异常高浓度的基因组区域。这些结合位点簇中有很大一部分与受这些因素调控的已知CRM重叠。此外，许多剩余的簇与以受这些因子调控的基因模式特征表达的基因相邻。我们测试了新发现的一个簇，定位在GAP基因巨人(GT)的上游，并表明它作为增强子重现了GT的后继表达模式。
A major challenge in interpreting genome sequences is understanding how the genome encodes the information that specifies when and where a gene will be expressed. The first step in this process is the identification of regions of the genome that contain regulatory information. In higher eukaryotes, this cis-regulatory information is organized into modular units [cis-regulatory modules (CRMs)] of a few hundred base pairs. A common feature of these cis-regulatory modules is the presence of multiple binding sites for multiple transcription factors. Here, we evaluate the extent to which the tendency for transcription factor binding sites to be clustered can be used as the basis for the computational identification of cis-regulatory modules. By using published DNA binding specificity data for five transcription factors active in the early Drosophila embryo, we identified genomic regions containing unusually high concentrations of predicted binding sites for these factors. A significant fraction of these binding site clusters overlap known CRMs that are regulated by these factors. In addition, many of the remaining clusters are adjacent to genes expressed in a pattern characteristic of genes regulated by these factors. We tested one of the newly identified clusters, mapping upstream of the gap gene giant (gt), and show that it acts as an enhancer that recapitulates the posterior expression pattern of gt.