title: Organization of the mitotic chromosome.
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.
authors.affiliation: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School (UMMS), 368 Plantation Street, Worcester, MA 01605-0103, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Naumova
authors.forename: Maxim
authors.initials: M
authors.lastname: Imakaev
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Fudenberg
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhan
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Lajoie
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Mirny
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
mesh_terms: D001704:Biopolymers / Q000737:chemistry; D002453:Cell Cycle / Q000235:genetics; D002843:Chromatin / Q000737:chemistry; D002891:Chromosomes, Human, Pair 21 / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000235:genetics; D008938:Mitosis / Q000235:genetics*; D008956:Models, Chemical
chemical_list: D001704:Biopolymers; D002843:Chromatin