title: Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion.
abstract: Nucleosome placement, or DNA linker length patterns, are believed to yield specific spatial features in chromatin fibers, but details are unknown. Here we examine by mesoscale modeling how kilobase (kb) range contacts and fiber looping depend on linker lengths ranging from 18 to 45 bp, with values modeled after living systems, including nucleosome free regions (NFRs) and gene encoding segments. We also compare artificial constructs with alternating versus randomly distributed linker lengths in the range of 18-72 bp. We show that nonuniform distributions with NFRs enhance flexibility and encourage kb-range contacts. NFRs between neighboring gene segments diminish short-range contacts between flanking nucleosomes, while enhancing kb-range contacts via hierarchical looping. We also demonstrate that variances in linker lengths enhance such contacts. In particular, moderate sized variations in fiber linker lengths (∼27 bp) encourage long-range contacts in randomly distributed linker length fibers. Our work underscores the importance of linker length patterns, alongside bound proteins, in biological regulation. Contacts formed by kb-range chromatin folding are crucial to gene activity. Because we find that special linker length distributions in living systems promote kb contacts, our work suggests ways to manipulate these patterns for regulation of gene activity.
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square E, New York, New York 10003, United States.
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Bascom
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square E, New York, New York 10003, United States.
authors.forename: Taejin
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square E, New York, New York 10003, United States.|Courant Institute of Mathematical Sciences, New York University , 251 Mercer St, New York, New York 10012, United States.|New York University-East China Normal University Center for Computational Chemistry at New York University Shanghai , Room 340, Geography Building, North Zhongshan Road, 3663 Shanghai, China.
authors.forename: Tamar
authors.identifier: 0000-0002-2392-2062
authors.initials: T
authors.lastname: Schlick
mesh_terms: D000465:Algorithms; D002843:Chromatin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D004247:DNA