We show that the mechanism by which chromatin displaying higher-order
structure is usually isolated from nuclei involves a transition to an
extended nucleosomal arrangement. After being released from nuclei, ch
romatin must refold in order to produce the typical chromatin fibers o
bserved in solution. For starfish sperm chromatin with a long nucleoso
me repeat (222 bp), isolated fibers are significantly wider than those
in the nucleus, indicating that the refolding process does not regene
rate the native higher-order structure. We also propose that for typic
al eukaryotic nuclei, the concept that the native state of the (inacti
ve) bulk of the genome is a chromatin fiber with defined architecture
be reconsidered.