High-throughput localization of functional elements by quantitative chromatin profiting
High-throughput localization of functional elements by quantitative chromatin profiting
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DOI：
10.1038/nmeth721
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发表时间：
2004-12-01
期刊：
影响因子：
48
通讯作者：
Stamatoyannopoulos, JA
中科院分区：
文献类型：
--
作者：
Dorschner, M;Hawrylycz, M;Stamatoyannopoulos, JA
鉴定在复杂基因组背景下调节转录的功能性非编码元件是现代生物学的主要目标。将功能定位到特定序列是遗传和计算研究的要求。在这里，我们描述了一个通用的方法，定量染色质获利，使用在体内染色质结构的定量分析，在整个基因位点，快速，准确地定位顺式调节序列和其他功能模式编码的DNase I超敏位点。为了证明这种方法的准确性，我们分析了类似于300 kitobases的人类基因组序列从不同的基因位点和干净划定的功能元件对应的一个频谱的经典顺式调节活动，包括增强子，启动子，基因座控制区和绝缘体以及新的元素。系统的，高通量的功能元件与DNase I超敏位点的鉴定将大大扩展我们的转录调控的知识，并应简化与表型后果的非编码遗传变异的搜索。
Identification of functional, noncoding elements that regulate transcription in the context of complex genomes is a major goal of modern biology. Localization of functionality to specific sequences is a requirement for genetic and computational studies. Here, we describe a generic approach, quantitative chromatin profiting, that uses quantitative analysis of in vivo chromatin structure over entire gene loci to rapidly and precisely localize cis-regutatory sequences and other functional modalities encoded by DNase I hypersensitive sites. To demonstrate the accuracy of this approach, we analyzed similar to 300 kitobases of human genome sequence from diverse gene loci and cleanly delineated functional elements corresponding to a spectrum of classical cis-regutatory activities including enhancers, promoters, Locus control regions and insulators as well as novel elements. Systematic, high-throughput identification of functional elements coinciding with DNase I hypersensitive sites will substantially expand our knowledge of transcriptional regulation and should simplify the search for noncoding genetic variation with phenotypic consequences.