Cell-specific epigenetic regulation of ChM-I gene expression: crosstalk between DNA methylation and histone acetylation.
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.
Aoyama
Tomoki
T
Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. blue@frontier.kyoto-u.ac.jp
Okamoto
Takeshi
T
Kohno
Yoshiki
Y
Fukiage
Kenichi
K
Otsuka
Seiji
S
Furu
Moritoshi
M
Ito
Kinya
K
Jin
Yonghui
Y
Nagayama
Satoshi
S
Nakayama
Tomitaka
T
Nakamura
Takashi
T
Toguchida
Junya
J
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
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