Link to dataset related to article "Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells"

Accessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). While stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of <em>cis</em>-regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown. Here, we devised a novel quantitative framework discriminating different types of nucleosome remodeling events in micrococcal nuclease ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) data sets and used it to analyze nucleosome dynamics at stimulus-regulated <em>cis</em>-regulatory elements. At enhancers, remodeling preferentially affected poorly positioned nucleosomes while sparing well-positioned nucleosomes flanking the enhancer core, indicating that inducible TFs do not suffice to overrule basal nucleosomal organization maintained by lineage-determining TFs. Remodeling events appeared to be combinatorially driven by multiple TFs, with distinct TFs showing, however, different remodeling efficiencies. Overall, these data provide a systematic view of the impact of stimulation on nucleosome organization and genome accessibility in mammalian cells.基因组调控信息的可及性，主要由转录因子（transcription factors, TFs）的核小体组织活性所调控。尽管刺激诱导型转录因子可结合由谱系决定性转录因子维持开放状态的基因组区域，但其同时还可增强数千个顺式（cis）调控元件的可及性。此类染色质开放改变背后的核小体重塑事件，及其与核小体基础定位的相互作用机制迄今尚不明确。本研究构建了一种全新的定量分析框架，可区分微球菌核酸酶染色质免疫共沉淀结合高通量测序（micrococcal nuclease ChIP-seq）数据集内的不同类型核小体重塑事件，并利用该框架分析了刺激应答型顺式调控元件处的核小体动态变化。在增强子区域，核小体重塑优先作用于定位松散的核小体，而不影响增强子核心侧翼定位良好的核小体，这表明诱导型转录因子不足以推翻由谱系决定性转录因子维持的基础核小体组织状态。核小体重塑事件似乎由多种转录因子组合驱动，但不同转录因子展现出各异的重塑效率。总体而言，本研究的数据为解析刺激信号对哺乳动物细胞内核小体组织状态及基因组可及性的影响提供了系统性视角。