The formation of such loops at least partly explains the reduction in chromosomal length during nuclear division. The central structure, visible only by immunofluorescence or upon denaturation, may simply reflect the axial concentration of putative scaffold components.įrom the chromosome’s central axis (proteinaceous or otherwise) radiate loops of chromatin, as demonstrated by classical cytologic studies of lampbrush chromosomes ( 9) and subsequently by electron microscopic studies of histone-depleted mitotic chromosomes ( 1). Indeed, while proteinaceous cores are readily apparent in meiotic chromosomes ( 8), extensive analysis by thin-section electron microscopy has failed to reveal a corresponding core in mitotic chromosomes ( 6). Others, however, have argued against the existence of a scaffold ( 6, 7). The concept has received recent support from chromosome conformation capture studies of mitotic cells ( 5). Biochemical analysis of the scaffold suggested a rather simple composition, dominated by two proteins ( 2), later identified as topoisomerase II ( 3) and condensin ( 4). The existence of a scaffold in the center of the mitotic chromosome was proposed long ago on the basis of electron micrographs of chromosomes depleted of most proteins, dehydrated in ethanol, and stained with uranyl acetate ( 1). By contrast, the physical basis for condensation has remained obscure, as have its cellular mediators. Length-wise contraction is thought to be explained by the formation of arrays of chromatin loops, radiating from the central axis. Axialization is thought to depend on the formation of a central proteinaceous “scaffold,” which has been convincingly demonstrated for meiotic chromosomes but remains contentious in the case of mitotic chromosomes. One sentence summary The mitotic chromosome is an axially scaffolded ionic hydrogel, undergoing a volume phase transition to achieve a condensed state.Įukaryotic chromosomes undergo several gross structural rearrangements during nuclear division: they axialize (adopting a cylindrical form), they contract length-wise, and they condense. These findings, together with classical cytology showing loops of chromatin, lead to the description of mitotic chromosome structure in terms of two simple principles: contraction of length of chromatin fibers by the formation of loops, radiating from a central axis and condensation of the chromosomal material against the central axis through a volume phase transition. The theory predicts a change of state (a “volume phase transition”) in the course of condensation, and such a transition was shown to occur. Established physico-chemical theory for ionic hydrogels was modified for application to chromosomal material and shown to accurately predict the observed condensation behavior. Computational methods were developed for the quantitative analysis of chromosome morphology in high throughput, enabling the recording of condensation behavior of thousands of individual chromosomes. Procedures were devised for the reversible decondensation and recondensation of purified mitotic chromosomes.

Pearson protein scaffold chromosome