Cryo-ET (cryo-electron tomography) is a powerful tool for studying the structure of biological objects in their native state. However, Cryo-ET is still not widely used to study cellular organelles including cell nucleus and chromatin in situ. In our work, we aimed to investigate the possibilities of employing cryo-ET for studying the architecture of natively preserved chromatin, focusing on the possibility of using a cryoCLEM (cryo-correlative light and electron microscopy) approach to target final steps of sample preparation by focused ion beam (FIB) milling exactly to the area of interest, namely, heterochromatin loci.
Kazakov et al. (Mon,) studied this question.