ChIP-seq accurately predicts tissue-specific activity of enhancers.
ChIP-seq accurately predicts tissue-specific activity of enhancers.
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DOI：
10.1038/nature07730
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发表时间：
2009-02-12
期刊：
影响因子：
64.8
通讯作者：
Pennacchio, Len A.
中科院分区：
文献类型：
--
作者：
Visel, Axel;Blow, Matthew J.;Li, Zirong;Zhang, Tao;Akiyama, Jennifer A.;Holt, Amy;Plajzer-Frick, Ingrid;Shoukry, Malak;Wright, Crystal;Chen, Feng;Afzal, Veena;Ren, Bing;Rubin, Edward M.;Pennacchio, Len A.
解码人类基因组的一个主要但尚未解决的问题是确定控制基因空间和时间表达的调控序列。远作用转录增强子的发现尤其具有挑战性，因为它们分散在基因组的大量非编码部分中。进化序列约束可以促进增强子的发现，但不能预测它们在体内何时何地活跃。在这里，我们展示了增强子相关蛋白p300的染色质免疫沉淀的结果，随后进行了大规模平行测序，并绘制了小鼠胚胎前脑、中脑和肢体组织中p300的数千个体内结合位点。我们在转基因小鼠实验中测试了86个这些序列，在几乎所有的情况下都显示了通过p300结合预测的组织中可重复的增强子活性。我们的研究结果表明，p300结合的体内定位是一种高度准确的识别增强子及其相关活性的方法，并表明这些数据集将有助于在全基因组范围内研究组织特异性增强子在人类生物学和疾病中的作用。
A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.
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