title: Histone H4 K16Q mutation, an acetylation mimic, causes structural disorder of its N-terminal basic patch in the nucleosome.
abstract: Histone tails and their posttranslational modifications play important roles in regulating the structure and dynamics of chromatin. For histone H4, the basic patch K(16)R(17)H(18)R(19) in the N-terminal tail modulates chromatin compaction and nucleosome sliding catalyzed by ATP-dependent ISWI chromatin remodeling enzymes while acetylation of H4 K16 affects both functions. The structural basis for the effects of this acetylation is unknown. Here, we investigated the conformation of histone tails in the nucleosome by solution NMR. We found that backbone amides of the N-terminal tails of histones H2A, H2B, and H3 are largely observable due to their conformational disorder. However, only residues 1-15 in H4 can be detected, indicating that residues 16-22 in the tails of both H4 histones fold onto the nucleosome core. Surprisingly, we found that K16Q mutation in H4, a mimic of K16 acetylation, leads to a structural disorder of the basic patch. Thus, our study suggests that the folded structure of the H4 basic patch in the nucleosome is important for chromatin compaction and nucleosome remodeling by ISWI enzymes while K16 acetylation affects both functions by causing structural disorder of the basic patch K(16)R(17)H(18)R(19).
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Bing-Rui
authors.initials: BR
authors.lastname: Zhou
authors.forename: Hanqiao
authors.initials: H
authors.lastname: Feng
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ghirlando
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kato
authors.forename: James
authors.initials: J
authors.lastname: Gruschus
authors.forename: Yawen
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000737:chemistry; D042002:Chromatin Assembly and Disassembly; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D006657:Histones / Q000737:chemistry* / Q000235:genetics*; D008239:Lysine / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D008239:Lysine