Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions.
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.
Muthurajan
Uma M
UM
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
Bao
Yunhe
Y
Forsberg
Lawrence J
LJ
Edayathumangalam
Rajeswari S
RS
Dyer
Pamela N
PN
White
Cindy L
CL
Luger
Karolin
K
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
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012965:Sodium Chloride; D004247:DNA; D008274:Magnesium