Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data.
Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data.
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从哺乳动物基因表达数据中发现组织特异性DNA序列基序的荟萃分析发现。
DOI：
10.1186/1471-2105-7-229
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发表时间：
2006-04-27
影响因子：
3
通讯作者：
Bulyk, Martha L.
中科院分区：
文献类型：
--
作者：
Huber, Bertrand R.;Bulyk, Martha L.
基因表达调控的一个关键步骤是转录因子（TFs）与它们的DNA识别位点的序列特异性结合。然而，即使采用跨物种序列保守性，在高等真核生物中阐明转录因子结合位点（TFBS）基序一直具有挑战性。我们假设对于人类和小鼠，在人类和小鼠基因表达数据中以相似的组织特异性方式表达的许多直系同源基因，很可能由结合到这些基因组之间保守的非编码序列内的DNA序列基序的直系同源转录因子共同调控。
我们在四种不同的基序发现算法中进行自动基序搜索和合并，然后对所得基序进行筛选，以找出那些包含信息含量模块的基序。将这种基序发现策略应用于共表达的组织特异性人类基因周围的保守非编码区域，使我们能够在我们所研究的所有18个组织特异性表达簇中发现先前已知的以及许多新的候选调控DNA基序。对于先前已知的TFBS基序，我们观察到如果一个转录因子在特定的感兴趣组织中表达，那么在大多数情况下我们能识别出一个与其TRANSFAC基序匹配的基序；相反，在所有那些与TRANSFAC基序匹配的已发现基序中，大多数相应的转录因子转录本在与发现该基序的表达簇相对应的组织中表达。
我们的结果表明，整合多种基序发现工具的结果比仅使用其中一种工具能识别出更多已知和新的基序，并对其进行更高的排序。此外，我们认为我们的同步富集策略有助于识别可能的人类顺式调控元件。许多已发现的基序可能对应于尚未表征的组织特异性转录因子的新结合位点基序。我们预计这种策略对于识别其他后生动物基因组中的基序是有用的。
A key step in the regulation of gene expression is the sequence-specific binding of transcription factors (TFs) to their DNA recognition sites. However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been challenging, even when employing cross-species sequence conservation. We hypothesized that for human and mouse, many orthologous genes expressed in a similarly tissue-specific manner in both human and mouse gene expression data, are likely to be co-regulated by orthologous TFs that bind to DNA sequence motifs present within noncoding sequence conserved between these genomes. We performed automated motif searching and merging across four different motif finding algorithms, followed by filtering of the resulting motifs for those that contain blocks of information content. Applying this motif finding strategy to conserved noncoding regions surrounding co-expressed tissue-specific human genes allowed us to discover both previously known, and many novel candidate, regulatory DNA motifs in all 18 tissue-specific expression clusters that we examined. For previously known TFBS motifs, we observed that if a TF was expressed in the specified tissue of interest, then in most cases we identified a motif that matched its TRANSFAC motif; conversely, of all those discovered motifs that matched TRANSFAC motifs, most of the corresponding TF transcripts were expressed in the tissue(s) corresponding to the expression cluster for which the motif was found. Our results indicate that the integration of the results from multiple motif finding tools identifies and ranks highly more known and novel motifs than does the use of just one of these tools. In addition, we believe that our simultaneous enrichment strategies helped to identify likely human cis regulatory elements. A number of the discovered motifs may correspond to novel binding site motifs for as yet uncharacterized tissue-specific TFs. We expect this strategy to be useful for identifying motifs in other metazoan genomes.
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影响因子：
64.8
作者：
Kellis, M;Patterson, N;Lander, ES
通讯作者：
Lander, ES
DOI：
10.1073/pnas.180265397
发表时间：
2000-08-29
影响因子：
11.1
作者：
Bussemaker, HJ;Li, H;Siggia, ED
通讯作者：
Siggia, ED
影响因子：
2.1
作者：
Hase, T;Yoshimura, R;Sano, H
通讯作者：
Sano, H
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM
影响因子：
14.9
作者：
Huang, HD;Horng, JT;Huang, SL
通讯作者：
Huang, SL