title: Partially Assembled Nucleosome Structures at Atomic Detail.
abstract: The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation. On average, the length of protected DNA in each structure is roughly 18 basepairs per histone protein. Atomistically detailed PANS are used to explain experimental observations; specifically, we discuss interpretation of atomic force microscopy, Förster resonance energy transfer, and small-angle x-ray scattering data obtained under conditions when PANS are expected to exist. Further, we suggest an alternative interpretation of a recent genome-wide study of DNA protection in active chromatin of fruit fly, leading to a conclusion that the three PANS are present in actively transcribing regions in a substantial amount. The presence of PANS may not only be a consequence, but also a prerequisite for fast transcription in vivo.
authors.affiliation: Division of Molecular and Radiation Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova Roscha, Gatchina, Leningrad District, Russia; Institute of Physics, Nanotechnology and Telecommunications, NRU Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
authors.forename: Georgy N
authors.initials: GN
authors.lastname: Rychkov
authors.affiliation: Division of Molecular and Radiation Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova Roscha, Gatchina, Leningrad District, Russia; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Ilatovskiy
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Nazarov
authors.affiliation: Division of Molecular and Radiation Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova Roscha, Gatchina, Leningrad District, Russia; Institute of Applied Mathematics and Mechanics, NRU Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Shvetsov
authors.affiliation: Division of Molecular and Radiation Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova Roscha, Gatchina, Leningrad District, Russia.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Lebedev
authors.affiliation: Division of Molecular and Radiation Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova Roscha, Gatchina, Leningrad District, Russia.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Konev
authors.affiliation: Division of Molecular and Radiation Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova Roscha, Gatchina, Leningrad District, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Isaev-Ivanov
authors.affiliation: Departments of Computer Science and Physics, Virginia Tech, Blacksburg, Virginia. Electronic address: alexey@cs.vt.edu.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Onufriev
mesh_terms: D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D023281:Genomics; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D009707:Nucleosomes; D004247:DNA