Revisiting the organization of Polycomb-repressed domains: 3D chromatin models from Hi-C compared with super-resolution imaging

The accessibility of target gene, a factor critical for gene regulation, is controlled by epigenetic fine-tuning of chromatin organization. While there are multiple experimental techniques to study change of chromatin architecture with its epigenetic state, measurements from them are not always complementary. A qualitative discrepancy is noted between recent super-resolution imaging studies, particularly on Polycomb-group protein repressed domains in Drosophila cell. One of the studies shows that Polycomb-repressed domains are more compact than inactive domains and are segregated from neighboring active domains, whereas Hi-C and chromatin accessibility assay as well as the other super-resolution imaging studies paint a different picture. To examine this issue in detail, we analyzed Hi-C libraries of Drosophila chromosomes as well as distance constraints from one of the imaging studies, and modeled different epigenetic domains by employing a polymer-based approach. According to our chromosome models, both Polycomb-repressed and inactive domains are featured with a similar degree of intra-domain packaging and significant intermixing with adjacent active domains. The epigenetic domains explicitly visualized by our polymer model call for extra attention to the discrepancy of the super-resolution imaging with other measurements, although its precise physicochemical origin still remains to be elucidated.