Extensive low-affinity transcriptional interactions in the yeast genome
Extensive low-affinity transcriptional interactions in the yeast genome
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DOI：
10.1101/gr.5113606
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发表时间：
2006-08-01
期刊：
影响因子：
7
通讯作者：
Tanay, Amos
中科院分区：
文献类型：
--
作者：
Tanay, Amos
主要的实验和计算工作的目标是基因组量表的转录网络的表征。许多研究的最终目标是通过明确定义的结合位点构建将转录因子与基因相关联的网络。除了在高亲和力结合位点发生的调节相互作用以外的其他调节相互作用在很大程度上被忽略了，并且尚未得到充分理解。在这里，我表明低亲和力相互作用在体内丰富，并且可以根据当前的高通量芯片实验进行量化。我开发的算法可以从序列和芯片数据中预测广泛动态范围的DNA结合能，并使用它们来揭示低亲和力转录因子结合的广泛功能。进化分析表明，即使在缺乏经典结合位点的启动子中，许多转录因子的结合能也保存下来。基因表达分析表明，这种启动子可以产生明显的表达。我估计，尽管只有一小部分基因组受到典型转录因子的强烈调节，但最多可能涉及较弱的相互作用。因此，低亲和力的转录因子-DNA相互作用在进化和功能上可能都很重要。
Major experimental and computational efforts are targeted at the characterization of transcriptional networks on a genomic scale. The ultimate goal of many of these studies is to construct networks associating transcription factors with genes via well-defined binding sites. Weaker regulatory interactions other than those occurring at high-affinity binding sites are largely ignored and are not well understood. Here I show that low-affinity interactions are abundant in vivo and quantifiable from current high-throughput ChIP experiments. I develop algorithms that predict DNA-binding energies from sequences and ChIP data across a wide dynamic range of affinities and use them to reveal widespread functionality of low-affinity transcription factor binding. Evolutionary analysis suggests that binding energies of many transcription factors are conserved even in promoters lacking classical binding sites. Gene expression analysis shows that such promoters can generate significant expression. I estimate that while only a small percentage of the genome is strongly regulated by a typical transcription factor, up to an order of magnitude more may be involved in weaker interactions. Low-affinity transcription factor-DNA interaction may therefore be important both evolutionarily and functionally.