title: Single-base resolution mapping of H1-nucleosome interactions and 3D organization of the nucleosome.
abstract: Despite the key role of the linker histone H1 in chromatin structure and dynamics, its location and interactions with nucleosomal DNA have not been elucidated. In this work we have used a combination of electron cryomicroscopy, hydroxyl radical footprinting, and nanoscale modeling to analyze the structure of precisely positioned mono-, di-, and trinucleosomes containing physiologically assembled full-length histone H1 or truncated mutants of this protein. Single-base resolution *OH footprinting shows that the globular domain of histone H1 (GH1) interacts with the DNA minor groove located at the center of the nucleosome and contacts a 10-bp region of DNA localized symmetrically with respect to the nucleosomal dyad. In addition, GH1 interacts with and organizes about one helical turn of DNA in each linker region of the nucleosome. We also find that a seven amino acid residue region (121-127) in the COOH terminus of histone H1 was required for the formation of the stem structure of the linker DNA. A molecular model on the basis of these data and coarse-grain DNA mechanics provides novel insights on how the different domains of H1 interact with the nucleosome and predicts a specific H1-mediated stem structure within linker DNA.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Université Joseph Fourier-Grenoble, Grenoble Cedex 9, France.
authors.forename: Sajad Hussain
authors.initials: SH
authors.lastname: Syed
authors.forename: Damien
authors.initials: D
authors.lastname: Goutte-Gattat
authors.forename: Nils
authors.initials: N
authors.lastname: Becker
authors.forename: Sam
authors.initials: S
authors.lastname: Meyer
authors.forename: Manu Shubhdarshan
authors.initials: MS
authors.lastname: Shukla
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hayes
authors.forename: Ralf
authors.initials: R
authors.lastname: Everaers
authors.forename: Dimitar
authors.initials: D
authors.lastname: Angelov
authors.forename: Jan
authors.initials: J
authors.lastname: Bednar
authors.forename: Stefan
authors.initials: S
authors.lastname: Dimitrov
mesh_terms: D000595:Amino Acid Sequence; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017665:Hydroxyl Radical / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding
chemical_list: D006657:Histones; D009707:Nucleosomes; D017665:Hydroxyl Radical
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9738-43
references.pmid: 9707545
references.citation: J Comput Chem. 2004 Oct;25(13):1605-12
references.pmid: 15264254
references.citation: Science. 1996 Oct 25;274(5287):614-7
references.pmid: 8849453
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5697-702
references.pmid: 15821029
references.citation: Nat Struct Mol Biol. 2006 Mar;13(3):250-5
references.pmid: 16462749
references.citation: J Biol Chem. 1996 Oct 18;271(42):25817-22
references.pmid: 8824211
references.citation: Trends Biochem Sci. 2008 Jun;33(6):247-53
references.pmid: 18468442
references.citation: EMBO J. 1988 Dec 1;7(12):3685-91
references.pmid: 3208745
references.citation: Nature. 1980 Dec 25;288(5792):675-9
references.pmid: 7453800
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8384-9
references.pmid: 16717183
references.citation: J Mol Biol. 1986 Feb 20;187(4):569-80
references.pmid: 3712436
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8210-5
references.pmid: 15928086
references.citation: EMBO J. 1987 Aug;6(8):2387-92
references.pmid: 2444434
references.citation: J Mol Biol. 1996 Mar 22;257(1):30-42
references.pmid: 8632457
references.citation: Nature. 1998 Sep 24;395(6700):402-5
references.pmid: 9759733
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14173-8
references.pmid: 9826673
references.citation: Nature. 1988 Apr 14;332(6165):663-4
references.pmid: 2833707
references.citation: Bioessays. 1999 May;21(5):367-71
references.pmid: 10376007
references.citation: Eur J Biochem. 1987 Sep 1;167(2):321-6
references.pmid: 3622517
references.citation: Nature. 1997 Sep 18;389(6648):251-60
references.pmid: 9305837
references.citation: Mol Cell Biol. 1998 Mar;18(3):1156-62
references.pmid: 9488430
references.citation: Biochemistry. 1994 Sep 20;33(37):11079-86
references.pmid: 7727360
references.citation: Biochemistry. 1978 Dec 12;17(25):5524-31
references.pmid: 728412
references.citation: Nucleic Acids Res. 1989 Dec 11;17(23):10069-81
references.pmid: 2602113