5.4 Conclusion

We demonstrated that TF binding signals of ChIP-seq experiments at CTCF motifs are predictive for chromatin looping. We provided a method, 7C, that is simple to use and integrates these signals with genomic sequence features to predict long-range chromatin contacts from single ChIP-seq experiments. 7C is freely available as R package (https://ibn-salem.github.io/sevenC/). The analysis of ChIP-seq experiments for 124 different TFs highlighted the role of cohesin, ZNF143 and CTCF in chromatin loop formation, but also suggested many other TFs, such as TRIM22, RUNX3, and BHLHE40, to be functionally involved in chromatin looping, likely in cooperation and protein interaction (direct or indirect) with CTCF at loop anchors.

Since our method needs only a single ChIP-seq experiment as input, it enables the analysis of chromatin interactions in diverse cell types and conditions, where Hi-C like data is not available. Therefore, 7C can be used to enable condition specific associations of distal TF binding sites and enhancers to promoters of target genes. These might allow the interpretation of non-coding genetic variants by genes in physical contact with the variant loci in a specific cell type or condition of interest. Furthermore, 7C might improve the resolution of Hi-C interaction maps by facilitating base-pair specific pairing of CTCF motifs located in bins of several kb. With these applications, 7C increases the value of ChIP-seq datasets, which now can be used to improve the analysis of 3D genome folding and their dynamic changess between diverse cell types and conditions.