title: Micron-scale coherence in interphase chromatin dynamics.
abstract: Chromatin structure and dynamics control all aspects of DNA biology yet are poorly understood, especially at large length scales. We developed an approach, displacement correlation spectroscopy based on time-resolved image correlation analysis, to map chromatin dynamics simultaneously across the whole nucleus in cultured human cells. This method revealed that chromatin movement was coherent across large regions (4-5 µm) for several seconds. Regions of coherent motion extended beyond the boundaries of single-chromosome territories, suggesting elastic coupling of motion over length scales much larger than those of genes. These large-scale, coupled motions were ATP dependent and unidirectional for several seconds, perhaps accounting for ATP-dependent directed movement of single genes. Perturbation of major nuclear ATPases such as DNA polymerase, RNA polymerase II, and topoisomerase II eliminated micron-scale coherence, while causing rapid, local movement to increase; i.e., local motions accelerated but became uncoupled from their neighbors. We observe similar trends in chromatin dynamics upon inducing a direct DNA damage; thus we hypothesize that this may be due to DNA damage responses that physically relax chromatin and block long-distance communication of forces.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zidovska
authors.forename: David A
authors.initials: DA
authors.lastname: Weitz
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchison
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase; D008958:Models, Molecular; D013057:Spectrum Analysis
chemical_list: D002843:Chromatin; D006657:Histones; D049452:Green Fluorescent Proteins
keywords: active materials; self-organization; soft matter
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