title: Nucleosomes in solution exist as a mixture of twist-defect states.
abstract: The 2.0 A crystal structure of a nucleosome core particle in complex with a bivalent pyrrole-imidazole polyamide reveals that this "clamp" effectively crossbraces the two gyres of the DNA superhelix, thereby stabilizing the nucleosome against dissociation. Using X-ray crystallography and footprinting techniques, we show that the clamp preferentially binds nucleosomes over free DNA, and that nucleosomal DNA exists as a mixture of multiple twist-defect intermediates in solution. The nucleosomes exist in one of two different conformations in various crystal structures that trap twist-defect intermediates, even on a strong positioning sequence. Evidence has been obtained supporting the existence of twist-defect states in nucleosomal DNA in solution that are similar to those obtained in crystal structures. Our results also substantiate the idea that twist diffusion may represent an important means of altering the accessibility of nucleosomal DNA both in the presence and in the absence of ATP-dependent chromatin-remodelling enzymes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
authors.forename: Rajeswari S
authors.initials: RS
authors.lastname: Edayathumangalam
authors.forename: Philipp
authors.initials: P
authors.lastname: Weyermann
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan
authors.forename: Joel M
authors.initials: JM
authors.lastname: Gottesfeld
authors.forename: Karolin
authors.initials: K
authors.lastname: Luger
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D009757:Nylons / Q000737:chemistry / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism; D012996:Solutions / Q000737:chemistry*; D014982:Xenopus laevis
chemical_list: D007093:Imidazoles; D009707:Nucleosomes; D009757:Nylons; D011758:Pyrroles; D012996:Solutions; D004247:DNA