title: Genome-wide profiling of nucleosome sensitivity and chromatin accessibility in Drosophila melanogaster.
abstract: Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNase-sensitive and MNase-resistant. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas MNase-sensitive nucleosomes form on A/T-rich sequences found at transcription start and termination sites, enhancers and DNase I hypersensitive sites. Estimates of nucleosome formation energies indicate that MNase-sensitive nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a decrease in cell growth temperature of about 10°C makes MNase-sensitive nucleosomes less accessible, suggesting that observed variations in MNase sensitivity are related to either thermal fluctuations of chromatin fibers or the activity of enzymatic machinery. In the vicinity of active genes and DNase I hypersensitive sites nucleosomes are organized into periodic arrays, likely due to 'phasing' off potential barriers formed by DNA-bound factors or by nucleosomes anchored to their positions through external interactions. The latter idea is substantiated by our biophysical model of nucleosome positioning and energetics, which predicts that nucleosomes immediately downstream of transcription start sites are anchored and recapitulates nucleosome phasing at active genes significantly better than sequence-dependent models.
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Răzvan V
authors.initials: RV
authors.lastname: Chereji
authors.affiliation: Department of Biochemistry, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Tsung-Wai
authors.initials: TW
authors.lastname: Kan
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, 9713AD, The Netherlands.
authors.forename: Magda K
authors.initials: MK
authors.lastname: Grudniewska
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk 630090, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Romashchenko
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, 9713AD, The Netherlands.
authors.forename: Eugene
authors.initials: E
authors.lastname: Berezikov
authors.affiliation: Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk 630090, Russia.
authors.forename: Igor F
authors.initials: IF
authors.lastname: Zhimulev
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, 9713AD, The Netherlands.
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.affiliation: Department of Physics and Astronomy and BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, NJ 08854, USA morozov@physics.rutgers.edu.
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Morozov
authors.affiliation: Department of Biochemistry, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk 630090, Russia Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk 630090, Russia yury.moshkin@gmail.com.
authors.forename: Yuri M
authors.initials: YM
authors.lastname: Moshkin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D020869:Gene Expression Profiling; D016678:Genome; D009707:Nucleosomes / Q000378:metabolism*
chemical_list: D002843:Chromatin; D009707:Nucleosomes