title: Chromosomes Progress to Metaphase in Multiple Discrete Steps via Global Compaction/Expansion Cycles.
abstract: Mammalian mitotic chromosome morphogenesis was analyzed by 4D live-cell and snapshot deconvolution fluorescence imaging. Prophase chromosomes, whose organization was previously unknown, are revealed to comprise co-oriented sister linear loop arrays displayed along a single, peripheral, regularly kinked topoisomerase II/cohesin/condensin II axis. Thereafter, rather than smooth, progressive compaction as generally envisioned, progression to metaphase is a discontinuous process involving chromosome expansion as well as compaction. At late prophase, dependent on topoisomerase II and with concomitant cohesin release, chromosomes expand, axes split and straighten, and chromatin loops transit to a radial disposition around now-central axes. Finally, chromosomes globally compact, giving the metaphase state. These patterns are consistent with the hypothesis that the molecular events of chromosome morphogenesis are governed by accumulation and release of chromosome stress, created by chromatin compaction and expansion. Chromosome state could evolve analogously throughout the cell cycle.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Zhangyi
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Institut de Génétique and Microbiologie, Université Paris-sud, 91405 Orsay Cedex, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Zickler
authors.affiliation: Deparment of Physics, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Prentiss
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Chang
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Witz
authors.affiliation: National Institute of Genetics and Graduate University for Advanced Studies (Sokendai), Mishima, Shizuoka 411-8540, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeshima
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: kleckner@fas.harvard.edu.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kleckner
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D033481:Chromosomes, Mammalian / Q000737:chemistry / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D003670:Deer; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D008856:Microscopy, Fluorescence; D008938:Mitosis; D046912:Multiprotein Complexes / Q000032:analysis; D013552:Swine; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D000097722:Cohesins; C108312:condensin complexes