Advances in Chromatin Imaging at Kilobase-Scale Resolution

It is now widely appreciated that the spatial organization of the genome is nonrandom, and its complex 3D folding has important consequences for many genome processes. Recent developments in multiplexed, super-resolution microscopy have enabled an unprecedented view of the polymeric structure of chromatin - from the loose folds of whole chromosomes to the detailed loops of cis-regulatory elements that regulate gene expression. Facilitated by the use of robotics, microfluidics, and improved approaches to super-resolution, thousands to hundreds of thousands of individual cells can now be analyzed in an individual experiment. This has led to new insights into the nature of genomic structural features identified by sequencing, such as topologically associated domains (TADs), and the nature of enhancer-promoter interactions underlying transcriptional regulation. We review these recent improvements.