title: Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X.
abstract: Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones.
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Japan PhD Program of Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan mokuwaki@md.tsukuba.ac.jp.
authors.forename: Mitsuru
authors.identifier: http://orcid.org/0000-0003-2118-442X
authors.initials: M
authors.lastname: Okuwaki
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Japan PhD Program of Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Abe
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Hisaoka
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002466:Cell Nucleolus / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D000072417:Protein Domains; D012335:RNA, Ribosomal / Q000378:metabolism
chemical_list: D056488:Histone Chaperones; D006657:Histones; D012335:RNA, Ribosomal; D004247:DNA