title: Nano-scale analyses of the chromatin decompaction induced by histone acetylation.
abstract: The acetylation of histone tails is a key factor in the maintenance of chromatin dynamics and cellular homeostasis. The hallmark of active chromatin is the hyper-acetylation of histones, which appears to result in a more open chromatin structure. Although short nucleosomal arrays have been studied, the structural dynamics of relatively long acetylated chromatin remain unclear. We have analyzed in detail the structure of long hyper-acetylated chromatin fibers using atomic force microscopy (AFM). Hyper-acetylated chromatin fibers isolated from nuclei that had been treated with Trichostatin A (TSA), an inhibitor of histone deacetylase, were found to be thinner than those from untreated nuclei. The acetylated chromatin fibers were more easily spread out of nuclei by high-salt treatment, implying that hyper-acetylation facilitates the release of chromatin fibers from compact heterochromatin regions. Chromatin fibers reconstituted in vitro from core histones and linker histone H1 became thinner upon acetylation. AFM imaging indicated that the gyration radius of the nucleosomal fiber increased after acetylation and that the hyper-acetylated nucleosomes did not aggregate at high salt concentrations, in contrast to the behavior of non-acetylated nucleosomal arrays, suggesting that acetylation increases long-range repulsions between nucleosomes. Based on these data, we considered a simple coarse grained model, which underlines the effect of remaining electric charges inside the chromatin fiber.
authors.affiliation: Laboratory of Plasma Membrane and Nuclear Signaling, Graduate School of Biostudies, Kyoto University. Kyoto, Japan. khizume@lab.nig.ac.jp
authors.forename: Kohji
authors.initials: K
authors.lastname: Hizume
authors.forename: Sumiko
authors.initials: S
authors.lastname: Araki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hata
authors.forename: Eloise
authors.initials: E
authors.lastname: Prieto
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Kunio
authors.initials: K
authors.lastname: Takeyasu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D005453:Fluorescence; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D036103:Nanotechnology; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009707:Nucleosomes; C012589:trichostatin A