title: Integrated molecular mechanism directing nucleosome reorganization by human FACT.
abstract: Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT-histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3-H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid-H2A steric collision on the H2A-docking surface of the H3-H4 tetramer within the nucleosome induces H2A-H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone.
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Sakyo-ku, Kyoto 606-8501, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoemachi, Sakyo-ku, Kyoto 606-8501, Japan; International Institute for Advanced Studies, Kizugawa-shi, Kyoto 619-0225, Japan;
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsunaka
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoemachi, Sakyo-ku, Kyoto 606-8501, Japan;
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Biotechnology, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan;
authors.forename: Takuji
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Developmental Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoemachi, Sakyo-ku, Kyoto 606-8501, Japan; International Institute for Advanced Studies, Kizugawa-shi, Kyoto 619-0225, Japan;
authors.forename: Kosuke
authors.initials: K
authors.lastname: Morikawa
mesh_terms: D003460:Crystallization; D003564:Cytidine Deaminase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D035602:Transcriptional Elongation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D006657:Histones; D009707:Nucleosomes; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: FACT; H2A–H2B displacement; chromatin remodeling; histone chaperone; nucleosome reorganization; transcription