Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster.
Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster.
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DOI：
10.1186/1471-2164-10-9
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发表时间：
2009-01-07
期刊：
影响因子：
4.4
通讯作者：
Halfon MS
中科院分区：
文献类型：
--
作者：
Zhu Q;Halfon MS
启动子是重要的转录顺式调控元件。除了作为基本转录装置的组装部位外，启动子还通过转录因子的差异结合和与远端增强子的选择性相互作用，在调节基因表达的时间和空间方面发挥关键作用。虽然许多基因有多个启动子，但很少有人关注这些启动子之间的相互关系；也没有太多的研究针对相邻基因的启动子之间的关系。我们对果蝇启动子进行了系统的研究。我们将启动子分为三类：唯一启动子、第一可选启动子(一个基因多个启动子中最多的5‘)和下游可选启动子(其余可选启动子3’至第一个)。我们观察到这三个类别之间不同的核苷酸分布和序列基序偏好。我们还研究了相邻基因的启动子，发现比预期数量更多的相邻基因具有相似的序列基序谱，这可能允许基因以协调的方式进行调控。与此一致的是，这些基因的相似启动子基序和相关基因表达谱之间存在正相关。我们的结果表明，不同的调控机制可能适用于三种启动子类别中的每一类，并为“基因表达邻域”提供了一种机制，即共表达基因的局部集群。总体而言，我们的数据揭示了启动子水平上基因组组织相对于替代启动子和邻近启动子的出乎意料的复杂性。
The promoter is a critical necessary transcriptional cis-regulatory element. In addition to its role as an assembly site for the basal transcriptional apparatus, the promoter plays a key part in mediating temporal and spatial aspects of gene expression through differential binding of transcription factors and selective interaction with distal enhancers. Although many genes have multiple promoters, little attention has been focused on how these relate to one another; nor has much study been directed at relationships between promoters of adjacent genes. We have undertaken a systematic investigation of Drosophila promoters. We divided promoters into three groups: unique promoters, first alternative promoters (the most 5' of a gene's multiple promoters), and downstream alternative promoters (the remaining alternative promoters 3' to the first). We observed distinct nucleotide distribution and sequence motif preferences among these three classes. We also investigated the promoters of neighboring genes and found that a greater than expected number of adjacent genes have similar sequence motif profiles, which may allow the genes to be regulated in a coordinated fashion. Consistent with this, there is a positive correlation between similar promoter motifs and related gene expression profiles for these genes. Our results suggest that different regulatory mechanisms may apply to each of the three promoter classes, and provide a mechanism for "gene expression neighborhoods," local clusters of co-expressed genes. As a whole, our data reveal an unexpected complexity of genomic organization at the promoter level with respect to both alternative and neighboring promoters.
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