Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.
Genome Res. 2011 Mar;21(3):456-64. doi: 10.1101/gr.112656.110. Epub 2010 Nov 24.
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.
不同细胞类型中的基因转录调控在很大程度上取决于转录因子结合的不同顺式作用元件。在这里，我们证明来自单个高通量 DNase I 超敏反应测定的数据可以描绘出数十万碱基分辨率的体内足迹，这些足迹可以精确地标示单个转录因子-DNA 相互作用。这些注释为顺式调控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，并且可以准确识别功能与非功能转录因子基序。我们还发现，足迹揭示了一种独特的进化保守模式，可将功能足迹碱基与周围 DNA 区分开来。最后，对 CTCF 足迹的详细分析表明存在多种结合模式以及主结合位点上游的新 DNA 结合基序。
