Super-resolution Imaging of Chromatin Nanostructure
Links Epigenetic State and 3D Genome Packaging
Metazoan genomes are packaged at multiple scales, and regulation of this spatial organization may play an important role in the developmental and cell fate selection. Unfortunately, current methods provide little information about 3D organization of the genome at the length scale of genes (kilobases) and regulatory domains (hundreds of kilobases) in single cells. I will present a new super-resolution imaging approach to study the structural organization of the genome at the kilobase to megabase scale in individual cells at 20 nm resolution. These domains largely occupy diffraction limited volumes and thus their structures cannot be resolved with conventional imaging approaches. From thousands of images of dozens of epigenetic domains from across the Drosophila genome, we have discovered, within a single cell type, a substantial diversity of structural patterns: compact and diffuse domains, branched and linear domains, domains that are highly entangled with one-another and domains which are strictly segregated. These different structural features are closely correlated to certain differences in the epigenetic state of the chromatin. I will focus on the organization of Polycomb bound domains, which exhibit a surprising, entangled structure and length-dependent compaction. Computational models suggest this organization could contribute to the repressive nature of the domains. Preliminary comparisons between developing tissues suggests differential regulation of chromatin structure associated with developmental fate selection. This work suggests further super-resolution imaging studies of chromatin structure at this scale may greatly aid our understanding of the role of genome structural regulation in development.