title: Cell-specific epigenetic regulation of ChM-I gene expression: crosstalk between DNA methylation and histone acetylation.
abstract: The expression of the chondromodulin-I (ChM-I) gene, a cartilage-specific gene, is regulated by the binding of Sp3 to the core promoter region, which is inhibited by the methylation of CpG in the target genome in the osteogenic lineage, osteosarcoma (OS) cells. The histone tails associated with the hypermethylated promoter region of the ChM-I gene were deacetylated by histone deacetylase 2 (HDAC2) in three ChM-I-negative OS cell lines. Treatment with an HDAC inhibitor induced the binding of Sp3 in one cell line, which became ChM-I-positive. This process was associated with acetylation instead of the dimethylation of histone H3 at lysine 9 (H3-K9) and, surprisingly, the demethylation of the core promoter region. The demethylation was transient, and gradually replaced by methylation after a rapid recovery of histone deacetylaion. These results represent an example of the plasticity of differentiation being regulated by the cell-specific plasticity of epigenetic regulation.
authors.affiliation: Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. blue@frontier.kyoto-u.ac.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Aoyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kohno
authors.forename: Kenichi
authors.initials: K
authors.lastname: Fukiage
authors.forename: Seiji
authors.initials: S
authors.lastname: Otsuka
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Furu
authors.forename: Kinya
authors.initials: K
authors.lastname: Ito
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Jin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagayama
authors.forename: Tomitaka
authors.initials: T
authors.lastname: Nakayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Junya
authors.initials: J
authors.lastname: Toguchida
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004261:DNA Replication; D044127:Epigenesis, Genetic; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051705:Sp3 Transcription Factor / Q000378:metabolism
chemical_list: D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; C497121:SP3 protein, human; C068675:CNMD protein, human; D051705:Sp3 Transcription Factor; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases