Large-scale discovery of promoter motifs in Drosophila melanogaster.
Large-scale discovery of promoter motifs in Drosophila melanogaster.
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大规模发现果蝇中的启动子图案。
DOI：
10.1371/journal.pcbi.0030007
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发表时间：
2007-01-19
影响因子：
4.3
通讯作者：
Hubbard TJ
中科院分区：
文献类型：
--
作者：
Down TA;Bergman CM;Su J;Hubbard TJ
理解基因调控的一个关键步骤是确定转录因子结合基序（TFBM）的组成部分，形成启动子和其他调控元件的构建块。通过实验鉴定这些基因是非常费力的，而且发现的TFBM的数量仍然相对较少，特别是与后生动物基因组中预测的数百个转录因子基因相比。我们已经使用了最近开发的统计基序发现方法，NestedMICA，检测候选TFBMs从一个大的果蝇启动子区域。在我们初步分析中推断的120个基序中，有25个与先前报道的基序在统计学上显著匹配，而87个似乎是新的。序列保守性和基序定位的分析表明，这些发现的基序中的绝大多数是预测基因组中的功能元件。许多基序与D.黑腹胚胎，我们能够获得我们的图案，包括八个新的图案的表达模式的信心注释。这些基序可以通过蒂芬获得，这是一个新的DNA序列基序数据库。我们已经发现了许多新的图案，在D。黑腹动物启动子区，并提供了几个独立的证据，这些是新的TFBM。我们的基序字典提供了一个坚实的基础，为进一步调查的调控元件在果蝇，并展示了技术，应适用于其他物种。我们认为，进一步改善计算基序发现应该缩小差距之间的已知基序集和后生动物基因组中的转录因子的总数。与编码蛋白质的基因组序列相反，人们对指导细胞何时何地激活给定基因的调控元件知之甚少。调控元件被认为是由短的DNA单词（基序）的集群，其中每个作为序列特异性DNA结合蛋白的结合位点。因此，建立一个全面的字典，这样的图案是一个重要的一步，更广泛地了解基因调控。使用最近发表的NestedMICA方法检测一组序列中的过度表达的基序，我们建立了一个120个基序的字典，从果蝇基因组中的调控序列，其中87个是新的。位置偏差的分析，跨物种的保护，并与果蝇胚胎中的基因表达的特定模式的关联表明，绝大多数这些新发现的图案代表功能调控元件。除了为研究最深入的模式生物之一提供初始基序字典外，这项工作还为全面发现复杂动物基因组中的调控基序提供了分析框架。
A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs) that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes. In contrast to the genomic sequences that encode proteins, little is known about the regulatory elements that instruct the cell as to when and where a given gene should be active. Regulatory elements are thought to consist of clusters of short DNA words (motifs), each of which acts as a binding site for sequence-specific DNA binding protein. Thus, building a comprehensive dictionary of such motifs is an important step towards a broader understanding of gene regulation. Using the recently published NestedMICA method for detecting overrepresented motifs in a set of sequences, we build a dictionary of 120 motifs from regulatory sequences in the fruitfly genome, 87 of which are novel. Analysis of positional biases, conservation across species, and association with specific patterns of gene expression in fruitfly embryos suggest that the great majority of these newly discovered motifs represent functional regulatory elements. In addition to providing an initial motif dictionary for one of the most intensively studied model organisms, this work provides an analytical framework for the comprehensive discovery of regulatory motifs in complex animal genomes.
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DOI：
10.1073/pnas.231608898
发表时间：
2002-01-22
影响因子：
11.1
作者：
Berman, BP;Nibu, Y;Eisen, MB
通讯作者：
Eisen, MB
影响因子：
5.8
作者：
Adryan, Boris;Teichmann, Sarah A.
通讯作者：
Teichmann, Sarah A.
影响因子：
5.8
作者：
Bergman, CM;Carlson, JW;Celniker, SE
通讯作者：
Celniker, SE
影响因子：
10.7
作者：
Dermitzakis, ET;Clark, AG
通讯作者：
Clark, AG
影响因子：
14.9
作者：
Drysdale RA;Crosby MA;FlyBase Consortium
通讯作者：
FlyBase Consortium