Electron microscopy, with its ability to image DNA and nucleosomes, can provide a key visual link in the understanding of chromatin conformation. We discuss applications of EM to current chromatin research with emphasis on strategies that eliminate many of the potential problems associated with conventional EM preparative techniques. Cryo-electron microscopy (cryo-EM) of isolated chromatin, whereby samples are imaged "in solution" in thin vitrified films, is considered in detail, with emphasis on the recovery of three-dimensional information and on its application to linker DNA conformation and to salt-induced compaction. Factors that currently limit the technique, and the prospects of overcoming them, are also considered.
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