Organization of the Mitotic Chromosome

TLDR

Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi‑C, across the cell cycle to reveal two distinct three‑dimensional folding states of the human genome. We show that the highly compartmentalized and cell type‑specific organization described previously for nonsynchronous cells is restricted to interphase, whereas in metaphase a homogeneous, locus‑independent folding state common to all chromosomes and cell types emerges, and polymer simulations indicate that metaphase Hi‑C data are inconsistent with classic hierarchical models but best described by a linearly organized, longitudinally compressed array of consecutive chromatin loops.

Abstract

Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.