Predicting functionality of protein-DNA interactions by integrating diverse evidence.
Predicting functionality of protein-DNA interactions by integrating diverse evidence.
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DOI：
10.1093/bioinformatics/btp213
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Workman CT
中科院分区：
文献类型：
--
作者：
Ucar D;Beyer A;Parthasarathy S;Workman CT
染色质免疫沉淀（ChIP-芯片）实验能够捕获体内调节蛋白和DNA之间的物理相互作用。然而，单独测量染色质结合不足以检测调控相互作用。检测到的结合事件可能不具有生物学相关性，或者在迄今为止检测的生长条件下可能未观察到已知的调控相互作用。为了正确识别转录因子（TF）和基因之间的物理相互作用，并确定其在各种实验条件下的调控意义，我们整合了ChIP芯片数据与基序结合位点，核小体占有率和mRNA表达数据集的概率框架内。该框架是专门为鉴定功能性和非功能性DNA结合事件而定制的。利用这一点，我们估计只有50%的条件特异性蛋白质-DNA结合在芽殖酵母是功能性的。我们进一步研究了在不同生长条件下决定蛋白质-DNA相互作用功能的分子因素。我们的分析表明，结合的功能是高度条件特异性和高度依赖于特定的辅因子的存在。因此，功能性和非功能性DNA结合的联合分析可能会为转录调控提供重要的新见解。联系人：workman@cbs.dtu.dk
Chromatin immunoprecipitation (ChIP-chip) experiments enable capturing physical interactions between regulatory proteins and DNA in vivo. However, measurement of chromatin binding alone is not sufficient to detect regulatory interactions. A detected binding event may not be biologically relevant, or a known regulatory interaction might not be observed under the growth conditions tested so far. To correctly identify physical interactions between transcription factors (TFs) and genes and to determine their regulatory implications under various experimental conditions, we integrated ChIP-chip data with motif binding sites, nucleosome occupancy and mRNA expression datasets within a probabilistic framework. This framework was specifically tailored for the identification of functional and non-functional DNA binding events. Using this, we estimate that only 50% of condition-specific protein–DNA binding in budding yeast is functional. We further investigated the molecular factors determining the functionality of protein–DNA interactions under diverse growth conditions. Our analysis suggests that the functionality of binding is highly condition-specific and highly dependent on the presence of specific cofactors. Hence, the joint analysis of both, functional and non-functional DNA binding, may lend important new insights into transcriptional regulation. Contact: workman@cbs.dtu.dk
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