Global mapping of protein-DNA interactions in vivo by digital genomic footprinting.
Global mapping of protein-DNA interactions in vivo by digital genomic footprinting.
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DOI：
10.1038/nmeth.1313
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发表时间：
2009-04
期刊：
影响因子：
48
通讯作者：
Stamatoyannopoulos, John A.
中科院分区：
文献类型：
--
作者：
Hesselberth, Jay R.;Chen, Xiaoyu;Zhang, Zhihong;Sabo, Peter J.;Sandstrom, Richard;Reynolds, Alex P.;Thurman, Robert E.;Neph, Shane;Kuehn, Michael S.;Noble, William S.;Fields, Stanley;Stamatoyannopoulos, John A.
在染色质的背景下，转录激活因子和阻遏因子与特定DNA序列的协调结合定义了真核基因组的调控程序。我们开发了一种数字化方法，通过使用大规模并行DNA测序对完整细胞核中的单个DNase I切割进行密集作图，来测定体内基因组DNA上的调节蛋白质占有率。对酿酒酵母基因组中> 2300万个裂解的分析揭示了数千个受保护的调节蛋白足迹，使得能够从头衍生因子结合基序以及鉴定数百个主要调节因子的新结合位点。我们观察到惊人的核苷酸水平DNase I切割模式和蛋白质-DNA相互作用之间的对应关系，由晶体学确定。这些数据还产生了更大的染色质特征的详细视图，包括定位的核小体侧翼因子结合区。数字基因组足迹法提供了一种强有力的方法来描绘任何生物体的顺式调控框架与可用的基因组序列。
The orchestrated binding of transcriptional activators and repressors to specific DNA sequences in the context of chromatin defines the regulatory program of eukaryotic genomes. We developed a digital approach to assay regulatory protein occupancy on genomic DNA in vivo by dense mapping of individual DNase I cleavages from intact nuclei using massively parallel DNA sequencing. Analysis of > 23 million cleavages across the Saccharomyces cerevisiae genome revealed thousands of protected regulatory protein footprints, enabling de novo derivation of factor binding motifs as well as the identification of hundreds of novel binding sites for major regulators. We observed striking correspondence between nucleotide-level DNase I cleavage patterns and protein-DNA interactions determined by crystallography. The data also yielded a detailed view of larger chromatin features including positioned nucleosomes flanking factor binding regions. Digital genomic footprinting provides a powerful approach to delineate the cis-regulatory framework of any organism with an available genome sequence.
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