title: High-throughput screening of genome fragments bound to differentially acetylated histones.
abstract: Although acetylation-deacetylation of histones contributes to regulation of gene expression, few methods have been available to determine the whole-genome histone acetylation profile in specific cells or tissues. We have now developed a genome-wide screening method, differential chromatin scanning (DCS), to isolate genome fragments embedded in histones subject to differential acetylation. This DCS screening was applied to a human gastric cancer cell line incubated with or without an inhibitor of histone deacetylase (HDAC) activity, resulting in the rapid identification of more than 250 genome fragments. Interestingly, a number of cancer-related genes were revealed to be the targets of HDAC in the cancer cells, including those for tumour protein 73 and cell division cycle 34. Such differential acetylation of histone was also shown to be linked to the regulation of transcriptional activity of the corresponding genes. Among the isolated genome fragments, 94% (32/34) of them were confirmed to be bound to differentially acetylated histones, and the genes corresponding to 78% (7/9) of them exhibited differential transcriptional activity consistent with the level of histone acetylation. With its high fidelity, the DCS method should open a possibility to rapidly compare the genome-wide histone acetylation profiles and to provide novel insights into molecular carcinogenesis.
authors.affiliation: Division of Functional Genomics, Jichi Medical School, 3311-1 Yakushiji, Kawachigun, Tochigi 329-0498, Japan.
authors.forename: Ruri
authors.initials: R
authors.lastname: Kaneda
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Koji
authors.initials: K
authors.lastname: Koinuma
authors.forename: Young Lim
authors.initials: YL
authors.lastname: Choi
authors.forename: Jun
authors.initials: J
authors.lastname: Ota
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kisanuki
authors.forename: Madoka
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000302:isolation & purification* / Q000378:metabolism*; D023281:Genomics / Q000379:methods*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D006657:Histones; D012333:RNA, Messenger; D004247:DNA