Schep Alicia N, Buenrostro Jason D, Denny Sarah K, Schwartz Katja, Sherlock Gavin, Greenleaf William J
Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
Biophysics Program, Stanford University School of Medicine, Stanford, California 94305, USA;
Genome Res. 2015 Nov;25(11):1757-70. doi: 10.1101/gr.192294.115. Epub 2015 Aug 27.
Transcription factors canonically bind nucleosome-free DNA, making the positioning of nucleosomes within regulatory regions crucial to the regulation of gene expression. Using the assay of transposase accessible chromatin (ATAC-seq), we observe a highly structured pattern of DNA fragment lengths and positions around nucleosomes in Saccharomyces cerevisiae, and use this distinctive two-dimensional nucleosomal "fingerprint" as the basis for a new nucleosome-positioning algorithm called NucleoATAC. We show that NucleoATAC can identify the rotational and translational positions of nucleosomes with up to base-pair resolution and provide quantitative measures of nucleosome occupancy in S. cerevisiae, Schizosaccharomyces pombe, and human cells. We demonstrate the application of NucleoATAC to a number of outstanding problems in chromatin biology, including analysis of sequence features underlying nucleosome positioning, promoter chromatin architecture across species, identification of transient changes in nucleosome occupancy and positioning during a dynamic cellular response, and integrated analysis of nucleosome occupancy and transcription factor binding.
转录因子通常结合无核小体的DNA，因此核小体在调控区域内的定位对于基因表达的调控至关重要。通过转座酶可及染色质分析（ATAC-seq），我们在酿酒酵母中观察到围绕核小体的DNA片段长度和位置的高度结构化模式，并将这种独特的二维核小体“指纹”作为一种名为NucleoATAC的新核小体定位算法的基础。我们表明，NucleoATAC可以以高达碱基对的分辨率识别核小体的旋转和平移位置，并提供酿酒酵母、裂殖酵母和人类细胞中核小体占有率的定量测量。我们展示了NucleoATAC在染色质生物学中一些突出问题上的应用，包括分析核小体定位背后的序列特征、跨物种的启动子染色质结构、识别动态细胞反应过程中核小体占有率和定位的瞬时变化，以及核小体占有率和转录因子结合的综合分析。
