Phylogenetically and spatially conserved word pairs associated with gene-expression changes in yeasts.

Phylogenetically and spatially conserved word pairs associated with gene-expression changes in yeasts.
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DOI:
10.1186/gb-2003-4-7-r43
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发表时间:
2003
期刊:
影响因子:
12.3
通讯作者:
Eisen MB
Eisen MB
中科院分区:
生物学1区
文献类型:
--
作者:
Chiang DY;Moses AM;Kellis M;Lander ES;Eisen MB

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保守序列的测定已经确定了单个转录因子结合位点。结合序列对的联合保守性和间隔限制预测了对基因表达的共同模式具有特异性的靶基因组。真核生物中的转录调控通常涉及多个转录因子结合到同一转录控制区,为了理解真核生物基因组的调控内容,有必要考虑单个结合位点的共现和空间关系。保守序列的测定(通常称为系统发育足迹法)已经确定了单个转录因子结合位点。我们将这一概念的功能保守的转录控制区的高阶功能。我们使用的基因组序列的酵母属的四种酵母,以确定潜在参与基因表达的多因素控制序列。我们发现了989个潜在的调控“模板”:在转录调控区共同保守的六聚体序列对,也表现出非随机的相对间距。这些模板中的许多单个序列对应于已知的转录因子结合位点,并且在其转录控制区中含有特定模板的基因组倾向于在已知相应转录因子具有活性的条件下差异表达。结合词对定义序列特征产生更具体的平均表达谱的预测和更翔实的全基因组表达数据的回归模型比单独考虑序列保守。结合序列对的联合保守性和间隔限制预测了对基因表达的共同模式具有特异性的靶基因组。我们的工作表明,位置信息,特别是转录因子结合位点之间的相对间距,可能代表了一个共同的组织原则的转录控制区。
The determination of conserved sequences has identified individual transcription factor binding sites. The incorporation of both joint conservation and spacing constraints of sequence pairs predicts groups of target genes that are specific for common patterns of gene expression. Transcriptional regulation in eukaryotes often involves multiple transcription factors binding to the same transcription control region, and to understand the regulatory content of eukaryotic genomes it is necessary to consider the co-occurrence and spatial relationships of individual binding sites. The determination of conserved sequences (often known as phylogenetic footprinting) has identified individual transcription factor binding sites. We extend this concept of functional conservation to higher-order features of transcription control regions. We used the genome sequences of four yeast species of the genus Saccharomyces to identify sequences potentially involved in multifactorial control of gene expression. We found 989 potential regulatory 'templates': pairs of hexameric sequences that are jointly conserved in transcription regulatory regions and also exhibit non-random relative spacing. Many of the individual sequences in these templates correspond to known transcription factor binding sites, and the sets of genes containing a particular template in their transcription control regions tend to be differentially expressed in conditions where the corresponding transcription factors are known to be active. The incorporation of word pairs to define sequence features yields more specific predictions of average expression profiles and more informative regression models for genome-wide expression data than considering sequence conservation alone. The incorporation of both joint conservation and spacing constraints of sequence pairs predicts groups of target genes that are specific for common patterns of gene expression. Our work suggests that positional information, especially the relative spacing between transcription factor binding sites, may represent a common organizing principle of transcription control regions.
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发表时间: 2002-01-22
影响因子: 11.1
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影响因子: 64.8
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