Institute of Cytology and Genetics, 630090 Novosibirsk, Russia.
Department of Natural Science, Novosibirsk State University, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2024 Jan 13;25(2):1011. doi: 10.3390/ijms25021011.
Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) is a central genome-wide method for in vivo analyses of DNA-protein interactions in various cellular conditions. Numerous studies have demonstrated the complex contextual organization of ChIP-seq peak sequences and the presence of binding sites for transcription factors in them. We assessed the dependence of the ChIP-seq peak score on the presence of different contextual signals in the peak sequences by analyzing these sequences from several ChIP-seq experiments using our fully enumerative GPU-based de novo motif discovery method, Argo_CUDA. Analysis revealed sets of significant IUPAC motifs corresponding to the binding sites of the target and partner transcription factors. For these ChIP-seq experiments, multiple regression models were constructed, demonstrating a significant dependence of the peak scores on the presence in the peak sequences of not only highly significant target motifs but also less significant motifs corresponding to the binding sites of the partner transcription factors. A significant correlation was shown between the presence of the target motifs FOXA2 and the partner motifs HNF4G, which found experimental confirmation in the scientific literature, demonstrating the important contribution of the partner transcription factors to the binding of the target transcription factor to DNA and, consequently, their important contribution to the peak score.
染色质免疫沉淀结合大规模平行 DNA 测序(ChIP-seq)是一种在各种细胞条件下进行体内 DNA-蛋白质相互作用的全基因组分析的核心方法。许多研究已经证明了 ChIP-seq 峰序列的复杂上下文组织以及转录因子结合位点的存在。我们通过使用我们的完全枚举 GPU 基于从头 motif 发现方法 Argo_CUDA 分析来自几个 ChIP-seq 实验的这些序列,评估了 ChIP-seq 峰得分对峰序列中不同上下文信号存在的依赖性。分析揭示了与靶标和伙伴转录因子结合位点相对应的一组显著 IUPAC motif。对于这些 ChIP-seq 实验,构建了多元回归模型,证明了峰得分的显著依赖性不仅取决于高度显著的靶标 motif 的存在,还取决于对应于伙伴转录因子结合位点的不太显著的 motif 的存在。靶标 motif FOXA2 和伙伴 motif HNF4G 的存在之间显示出显著的相关性,这在科学文献中得到了实验证实,证明了伙伴转录因子对靶标转录因子与 DNA 结合的重要贡献,因此它们对峰得分的重要贡献。