Contribution of transcription factor binding site motif variants to condition-specific gene expression patterns in budding yeast.

Contribution of transcription factor binding site motif variants to condition-specific gene expression patterns in budding yeast.
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DOI:
10.1371/journal.pone.0032274
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Li WH
Li WH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rest JS;Bullaughey K;Morris GP;Li WH

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现在,在实验上已经知道,顺式转录因子结合位点基序的变异序列可以促进基因的差异调节。我们通过分析表达微阵列数据和结合位点预测来描述基序变异和基因表达之间的关系。为了实现这一点,我们在统计上检测具有不同环境影响的基序变体。这种环境特异性可能是由于变体之间的亲和力差异,或者更可能的是,与这些变体结合的tf与辅因子的差异相互作用,以及不同环境中辅因子的差异存在。我们研究了四种酵母菌物种的功能变异的保守性,发现大约三分之一的转录因子具有以与不同基序位置的核苷酸相关的条件特异性方式差异表达的靶基因。我们发现我们的结果与实验文献中的一些案例(Reb1, Sum1, Mcm1和Rap1)有很好的一致性。这些结果和文献中越来越多的共识表明,基序变异可能在功能上经常是不同的,这可能在基因组数据中观察到,并且变异在特定条件的基因调控中起着重要作用。
It is now experimentally well known that variant sequences of a cis transcription factor binding site motif can contribute to differential regulation of genes. We characterize the relationship between motif variants and gene expression by analyzing expression microarray data and binding site predictions. To accomplish this, we statistically detect motif variants with effects that differ among environments. Such environmental specificity may be due to either affinity differences between variants or, more likely, differential interactions of TFs bound to these variants with cofactors, and with differential presence of cofactors across environments. We examine conservation of functional variants across four Saccharomyces species, and find that about a third of transcription factors have target genes that are differentially expressed in a condition-specific manner that is correlated with the nucleotide at variant motif positions. We find good correspondence between our results and some cases in the experimental literature (Reb1, Sum1, Mcm1, and Rap1). These results and growing consensus in the literature indicates that motif variants may often be functionally distinct, that this may be observed in genomic data, and that variants play an important role in condition-specific gene regulation.
G6PC2启动子的甲基化FOXA2结合位点中的单核苷酸多态性与体内胰岛素分泌有关,体外启动子活性增加。
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