Super-resolution fluorescence microscopy as a tool to study the nanoscale organization of chromosomes

Chromatin organization spans a wide range of structural complexity. Substructures at the 10–200 nm scale are poorly characterized, especially in living cells, due to the limitations of electron microscopy and standard optical microscopy. Recently developed super-resolution fluorescence microscopy methods represent an exciting opportunity to access those substructures, and recent progress with these techniques has yielded insights into chromatin organization at different condensation stages. Recent studies have focused on confronting the challenges that are specific to chromatin super-resolution imaging, such as the high packing density of mitotic chromosomes and difficulties in interpreting interphase chromatin images. Building on these first results and with ongoing rapid technical advances in super-resolution fluorescence imaging there is great potential to uncover new features with unprecedented detail.

► Chromatin substructures fall into a resolution gap between EM and optical microscopy.
► Super-resolution fluorescence microscopy is well suited to access these substructures.
► We review new insights into chromatin structure gained by super-resolution imaging.
► We discuss technical developments in super-resolution microscopy relevant to chromatin.