title: Complex of linker histone H5 with the nucleosome and its implications for chromatin packing.
abstract: Linker histones are essential for chromatin filament formation, and they play key roles in the regulation of gene expression. Despite the determination of structures of the nucleosome and linker histones, the location of the linker histone on the nucleosome is still a matter of debate. Here we show by computational docking that the globular domain of linker histone variant H5 (GH5) has three distinct DNA-binding sites, through which GH5 contacts the DNA at the nucleosome dyad and the linker DNA strands entering and exiting the nucleosome. Our results explain the extensive mutagenesis and crosslinking data showing that side chains spread throughout the GH5 surface interact with nucleosomal DNA. The nucleosome DNA contacts positively charged side chains that are conserved within the linker histone family, indicating that our model extends to linker histone-nucleosome interactions in general. Furthermore, our model provides a structural mechanism for formation of a dinucleosome complex specific to the linker histone H5, explaining its efficiency in chromatin compaction and transcription regulation. Thus, this work provides a basis for understanding how structural differences within the linker histone family result in functional differences, which in turn are important for gene regulation.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Roberts
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA