Ornithine decarboxylase antizyme induces hypomethylation of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2) in human oral cancer cell line

Takanori Tsuji, Daisuke Yamamoto, Kaori Shima, Kou Matsuo, Takashi Nishioka, Chang Yan Chen, Guo fu Hu, Akira Sasaki

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Methylation of CpG islands of genome DNA and lysine residues of histone H3 and H4 tails regulates gene transcription. Inhibition of polyamine synthesis by ornithine decarboxylase antizyme-1 (OAZ) in human oral cancer cell line resulted in accumulation of decarboxylated S-adenosylmethionine (dcSAM), which acts as a competitive inhibitor of methylation reactions. We anticipated that accumulation of dcSAM impaired methylation reactions and resulted in hypomethylation of genome DNA and histone tails. Methodology/Principal Findings: Global methylation state of genome DNA and lysine residues of histone H3 and H4 tails were assayed by Methylation by Isoschizomers (MIAMI) method and western blotting, respectively, in the presence or absence of OAZ expression. Ectopic expression of OAZ mediated hypomethylation of CpG islands of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2). Protein level of DNA methyltransferase 3B (DNMT3B) and histone H3K9me specific methyltransferase G9a were down-regulated in OAZ transfectant. Conclusions/Significance: OAZ induced hypomethylation of CpG islands of global genome DNA and H3K9me2 by down-regulating DNMT3B and G9a protein level. Hypomethylation of CpG islands of genome DNA and histone H3K9me2 is a potent mechanism of induction of the genes related to tumor suppression and DNA double strand break repair.

Original languageEnglish
Article numbere12554
Pages (from-to)1-8
Number of pages8
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 2010

Fingerprint

ornithine decarboxylase
Mouth Neoplasms
histones
Histones
Lysine
lysine
Genes
Methylation
Cells
cell lines
Genome
Cell Line
CpG Islands
genome
DNA
methylation
methyltransferases
Tail
S-adenosylmethionine
tail

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ornithine decarboxylase antizyme induces hypomethylation of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2) in human oral cancer cell line. / Tsuji, Takanori; Yamamoto, Daisuke; Shima, Kaori; Matsuo, Kou; Nishioka, Takashi; Chen, Chang Yan; Hu, Guo fu; Sasaki, Akira.

In: PLoS One, Vol. 5, No. 9, e12554, 2010, p. 1-8.

Research output: Contribution to journalArticle

Tsuji, Takanori ; Yamamoto, Daisuke ; Shima, Kaori ; Matsuo, Kou ; Nishioka, Takashi ; Chen, Chang Yan ; Hu, Guo fu ; Sasaki, Akira. / Ornithine decarboxylase antizyme induces hypomethylation of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2) in human oral cancer cell line. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-8.
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abstract = "Background: Methylation of CpG islands of genome DNA and lysine residues of histone H3 and H4 tails regulates gene transcription. Inhibition of polyamine synthesis by ornithine decarboxylase antizyme-1 (OAZ) in human oral cancer cell line resulted in accumulation of decarboxylated S-adenosylmethionine (dcSAM), which acts as a competitive inhibitor of methylation reactions. We anticipated that accumulation of dcSAM impaired methylation reactions and resulted in hypomethylation of genome DNA and histone tails. Methodology/Principal Findings: Global methylation state of genome DNA and lysine residues of histone H3 and H4 tails were assayed by Methylation by Isoschizomers (MIAMI) method and western blotting, respectively, in the presence or absence of OAZ expression. Ectopic expression of OAZ mediated hypomethylation of CpG islands of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2). Protein level of DNA methyltransferase 3B (DNMT3B) and histone H3K9me specific methyltransferase G9a were down-regulated in OAZ transfectant. Conclusions/Significance: OAZ induced hypomethylation of CpG islands of global genome DNA and H3K9me2 by down-regulating DNMT3B and G9a protein level. Hypomethylation of CpG islands of genome DNA and histone H3K9me2 is a potent mechanism of induction of the genes related to tumor suppression and DNA double strand break repair.",
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AU - Shima, Kaori

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AU - Hu, Guo fu

AU - Sasaki, Akira

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