title: Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions.
abstract: Here we describe 11 crystal structures of nucleosome core particles containing individual point mutations in the structured regions of histones H3 and H4. The mutated residues are located at the two protein-DNA interfaces flanking the nucleosomal dyad. Five of the mutations partially restore the in vivo effects of SWI/SNF inactivation in yeast. We find that even nonconservative mutations of these residues (which exhibit a distinct phenotype in vivo) have only moderate effects on global nucleosome structure. Rather, local protein-DNA interactions are disrupted and weakened in a subtle and complex manner. The number of lost protein-DNA interactions correlates directly with an increased propensity of the histone octamer to reposition with respect to the DNA, and with an overall destabilization of the nucleosome. Thus, the disruption of only two to six of the approximately 120 direct histone-DNA interactions within the nucleosome has a pronounced effect on nucleosome mobility and stability. This has implications for our understanding of how these structures are made accessible to the transcription and replication machinery in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
authors.forename: Uma M
authors.initials: UM
authors.lastname: Muthurajan
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Bao
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Forsberg
authors.forename: Rajeswari S
authors.initials: RS
authors.lastname: Edayathumangalam
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Dyer
authors.forename: Cindy L
authors.initials: CL
authors.lastname: White
authors.forename: Karolin
authors.initials: K
authors.lastname: Luger
mesh_terms: D002843:Chromatin / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D008274:Magnesium / Q000494:pharmacology; D008958:Models, Molecular; D009038:Motion; D009707:Nucleosomes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D017354:Point Mutation; D011487:Protein Conformation; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012965:Sodium Chloride; D004247:DNA; D008274:Magnesium