common folding motif variously referred to as topologically associating domains (TADs), or chromosomally interacting domains (CIDs) (Dixon et al. 2012; Nora et al. 2012; Sexton et al. 2012; Le et al. 2013; Mizuguchi et al. 2014; Hsieh et al. 2015; Wang et al. 2015). These domains are chromosomal regions that exhibit relatively high levels of self-association, with low levels of interactions being observed between adjacent TADs, and can be conceptualized as relatively unstructured “globules” or “crumples” of chromatin separated by boundaries. Finally, 3C methods have been used extensively to study enhancer-promoter interactions and other forms of long-distance loops, with a recent ∼1-kb-resolution study in mammalian cells identifying ∼10,000 loops between CTCF binding sites (Rao et al. 2014). Enhancer-promoter interactions typically occur within the boundaries of a TAD/CID and do not cross boundaries between TADs (Symmons et al. 2014). Many other variants of 3C exist, including methods such as ChIA-PET, in which an initial affinity step is used to isolate chromatin associated with factors such as RNA polymerase II or CTCF—the reduction in genomic complexity inherent in such enrichment provides much higher-resolution 3C data (at a given sequencing depth) for the interactions of interest (Li et al. 2012).
