title: Hinge and chromoshadow of HP1α participate in recognition of K9 methylated histone H3 in nucleosomes.
abstract: The majority of the genome in eukaryotes is packaged into transcriptionally inactive chromatin. Heterochromatin protein 1 (HP1) is a major player in the establishment and maintenance of heterochromatin. HP1 specifically recognizes a methylated lysine residue at position 9 in histone H3 through its N-terminal chromo domain (CD). To elucidate the binding properties of HP1α to nucleosomes in vitro, we reconstituted nucleosomes containing histone H3 trimethylated at lysine 9. HP1α exhibited high-affinity binding to nucleosomes containing methylated histone H3 in a nucleosome core-number-dependent manner. The hinge region (HR) connecting the CD and C-terminal chromoshadow domain (CSD), and the CSD contributed to the selective binding of HP1α to histone H3 with trimethylated lysine 9 through weak DNA binding and by suppressing the DNA binding, respectively. We propose that not only the specific recognition of lysine 9 methylation of histone H3 by the CD but also the HR and the CSD cooperatively contribute to the selective binding of HP1α to histone H3 lysine 9 methylated nucleosomes.
authors.affiliation: Laboratory of Epigenetics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mishima
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.forename: Toru
authors.initials: T
authors.lastname: Kawakami
authors.forename: Chanika D
authors.initials: CD
authors.lastname: Jayasinghe
authors.forename: Junji
authors.initials: J
authors.lastname: Otani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kikugawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishimura
authors.forename: Saburo
authors.initials: S
authors.lastname: Aimoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Tajima
authors.forename: Isao
authors.initials: I
authors.lastname: Suetake
mesh_terms: D000595:Amino Acid Sequence; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D009492:Neurospora crassa / Q000201:enzymology / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins; D017384:Sequence Deletion; D013379:Substrate Specificity
chemical_list: C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; D000090266:Chromobox Protein Homolog 5; D008239:Lysine