Peak Scores Significantly Depend on the Relationships between Contextual Signals in ChIP-Seq Peaks

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.