Understanding Chromatin Interactions By Model-Based Analysis of dCas9 Capture-3C-Seq Data

To detect chromatin interactions is important for understanding the fundamental regulatory landscape and organizational structures of chromosomes, and as well as the oversee behavior of regulatory DNA sequences that serve as potential drivers for diseases such as cancer. We presented a CAPTURE-3C-Seq approach to unbiasedly identify locus-specific long-range DNA interactions. Using an in vivo biotinylated nuclease-deficient Cas9 protein and sequence-specific guide RNAs, we show highresolution and selective isolation of chromatin interactions at a single-copy genomic locus. We provided Model-based pipelines to denoise and detect significant interactions. In situ capture of individual constituents of the enhancer cluster controlling human b-globin genes establishes evidence for composition-based hierarchical organization. Furthermore, unbiased analysis of chromatin interactions at disease-associated cis-elements and developmentally regulated super-enhancers reveals spatial features that causally control gene transcription.