title: Changing chromatin fiber conformation by nucleosome repositioning.
abstract: Chromatin conformation is dynamic and heterogeneous with respect to nucleosome positions, which can be changed by chromatin remodeling complexes in the cell. These molecular machines hydrolyze ATP to translocate or evict nucleosomes, and establish loci with regularly and more irregularly spaced nucleosomes as well as nucleosome-depleted regions. The impact of nucleosome repositioning on the three-dimensional chromatin structure is only poorly understood. Here, we address this issue by using a coarse-grained computer model of arrays of 101 nucleosomes considering several chromatin fiber models with and without linker histones, respectively. We investigated the folding of the chain in dependence of the position of the central nucleosome by changing the length of the adjacent linker DNA in basepair steps. We found in our simulations that these translocations had a strong effect on the shape and properties of chromatin fibers: i), Fiber curvature and flexibility at the center were largely increased and long-range contacts between distant nucleosomes on the chain were promoted. ii), The highest destabilization of the fiber conformation occurred for a nucleosome shifted by two basepairs from regular spacing, whereas effects of linker DNA changes of ?10 bp in phase with the helical twist of DNA were minimal. iii), A fiber conformation can stabilize a regular spacing of nucleosomes inasmuch as favorable stacking interactions between nucleosomes are facilitated. This can oppose nucleosome translocations and increase the energetic costs for chromatin remodeling. Our computational modeling framework makes it possible to describe the conformational heterogeneity of chromatin in terms of nucleosome positions, and thus advances theoretical models toward a better understanding of how genome compaction and access are regulated within the cell.
authors.affiliation: Institute for Applied Computer Science, University of Applied Sciences Stralsund, Stralsund, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Müller
authors.affiliation: Deutsches Krebsforschungszentrum and BioQuant, Heidelberg, Germany.
authors.forename: Nick
authors.initials: N
authors.lastname: Kepper
authors.affiliation: Institute for Applied Computer Science, University of Applied Sciences Stralsund, Stralsund, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schöpflin
authors.affiliation: Deutsches Krebsforschungszentrum and BioQuant, Heidelberg, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Ettig
authors.affiliation: Deutsches Krebsforschungszentrum and BioQuant, Heidelberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
authors.affiliation: Institute for Applied Computer Science, University of Applied Sciences Stralsund, Stralsund, Germany. Electronic address: gero.wedemann@fh-stralsund.de.
authors.forename: Gero
authors.initials: G
authors.lastname: Wedemann
mesh_terms: D002843:Chromatin / Q000737:chemistry*; D042002:Chromatin Assembly and Disassembly; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry; D006657:Histones / Q000737:chemistry; D008957:Models, Genetic; D008958:Models, Molecular; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry*; D018583:Pliability
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D004247:DNA