Helical Coiled Nucleosome Chromosome Architectures during Cell Cycle Progression

Abstract

AbstractRecent studies showed an interphase chromosome architecture, --- a specific coiled nucleosome structure, --- derived from cryo-preserved EM tomograms, and dispersed throughout the nucleus. The images were computationally processed to fill in the missing wedges of data caused by incomplete tomographic tilts. The resulting structures increased z-resolution enabling an extension of the proposed architecture to that of mitotic chromosomes.Here we provide additional insights and details into the coiled nucleosome chromosome architectures. We build on the defined chromosomes time-dependent structures in an effort to probe their dynamics. Variants of the coiled chromosome structures, possibly further defining specific regions, are discussed. We propose, based on generalized specific uncoiling of mitotic chromosomes in telophase, large-scale re-organization of interphase chromosomes. Chromosome territories, organized as micron-sized small patches, are constructed, satisfying complex volume considerations. Finally, we unveiled the structures of replicated coiled chromosomes, still attached to centromeres, as part of chromosome architecture.Significance StatementThis study places all 46 sequenced human chromosomes, --- correctly filled with nucleosomes and in micron sized chromosome territories — into 10micron (average sized) nuclei. The chromosome architecture used a helical nucleosome coiled structure discerned from cryo-EM tomography, as was recently published (https://doi.org/10.1073/pnas.2119101119). This chromosome architecture was further modeled to dynamic structures, structure variations and chromosome replication centromere complications. Finally, this chromosome architecture was modified to allow seamless transition through the cell cycle.