High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells
High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells
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DOI：
10.1101/gr.112656.110
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发表时间：
2011-03-01
期刊：
影响因子：
7
通讯作者：
Furey, Terrence S.
中科院分区：
文献类型：
--
作者：
Boyle, Alan P.;Song, Lingyun;Furey, Terrence S.
在不同的细胞类型中基因转录的调节主要由转录因子结合的不同的顺式元件组决定。在这里，我们证明，从一个单一的高通量DNase I超敏反应检测的数据可以描绘数十万的碱基对分辨率在人体细胞中的体内足迹，精确地标记个人的转录因子-DNA相互作用。这些注释为顺式调节元件的研究提供了独特的资源。我们发现特定转录因子的足迹与ChIP-seq富集相关，可以准确识别功能性与非功能性转录因子基序。我们还发现，足迹揭示了一个独特的进化保守模式，区分功能足迹基地从周围的DNA。最后，CTCF足迹的详细分析表明多种模式的结合和一个新的DNA结合基序上游的主要结合位点。
Regulation of gene transcription in diverse cell types is determined largely by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNase I hypersensitivity assay can delineate hundreds of thousands of base-pair resolution in vivo footprints in human cells that precisely mark individual transcription factor-DNA interactions. These annotations provide a unique resource for the investigation of cis-regulatory elements. We find that footprints for specific transcription factors correlate with ChIP-seq enrichment and can accurately identify functional versus nonfunctional transcription factor motifs. We also find that footprints reveal a unique evolutionary conservation pattern that differentiates functional footprinted bases from surrounding DNA. Finally, detailed analysis of CTCF footprints suggests multiple modes of binding and a novel DNA binding motif upstream of the primary binding site.