Extensive alterations in chromatin structure at the nucleosome level are linked to developmental potential. We hypothesize that such alterations in chromatin structure reflect and, to some extent, depend on the large-scale reorganization of the nuclear landscape. We have used electron spectroscopic imaging (ESI) to visualize chromatin organization at the mesoscale level of resolution in both pluripotent and differentiated cell types. Pluripotent cells are characterized by a highly dispersed mesh of 10-nm chromatin fibers that fill the nuclear volume. In contrast, differentiated cells display a propensity to form compact chromatin domains that lead to large regions of the nucleus devoid of DNA. Surprisingly, ESI combined with tomography methods reveals that the compact chromatin domains consist of 10-nm rather than 30-nm chromatin fibers. We propose that the transition between compact silent chromatin and open transcriptionally poised or active chromatin is based on the modulation of the packing density of 10-nm fibers rather than a transition between 10- and 30-nm fiber types.

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