title: Structural Mechanisms of Nucleosome Recognition by Linker Histones.
abstract: Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Bing-Rui
authors.initials: BR
authors.lastname: Zhou
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hanqiao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ghirlando
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: T Sam
authors.initials: TS
authors.lastname: Xiao
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: yawen@helix.nih.gov.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster; D006657:Histones / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry* / Q000502:physiology; D011485:Protein Binding
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D009707:Nucleosomes