Identification of an epigenetically silenced gene, RFX1, in human glioma cells using restriction landmark genomic scanning

Yohei Ohashi, Masakazu Ueda, Takeshi Kawase, Yutaka Kawakami, Masahiro Toda

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

To identify the CpG islands differentially methylated in human glioma, we performed restriction landmark genomic scanning with a CpG methylation-sensitive enzyme. We found 12 spots, the intensity of which was entirely lost or decreased in both the human glioma tissues examined as compared with that in matched normal lymphocytes, indicating aberrant methylation of these CpG islands in gliomas. The expression of RFX1, one of the genes associated with the methylated CpG islands, was frequently decreased in human glioma cell lines and tissues. We also demonstrated that the isolated CpG island located in the seventh intron of the RFX1 gene had enhancer activity and was hypermethylated in all of the glioma tissues and cell lines analysed, but not in normal brains or lymphocytes. Treatment of glioma cells with a demethylating agent, 5-azacytidine, resulted in the expression of RFX1, indicating that the silencing of the RFX1 gene may be attributable to its methylation. RFX1 has been implicated in transcriptional downregulation of the proto-oncogene c-myc. By expression of the RFX1 gene, the cellular proliferative activity of glioma cells was suppressed. Taken together, these results suggest that the RFX1 gene may be epigenetically silenced in human gliomas and involved in glioma tumorigenesis.

Original languageEnglish
Pages (from-to)7772-7779
Number of pages8
JournalOncogene
Volume23
Issue number47
DOIs
Publication statusPublished - 2004 Oct 14

Fingerprint

Glioma
CpG Islands
Genes
Methylation
Lymphocytes
Azacitidine
Cell Line
myc Genes
Gene Silencing
Introns
Carcinogenesis
Down-Regulation
Gene Expression
Brain
Enzymes

Keywords

  • Epigenetics
  • Glioma
  • Methylation
  • RFX1
  • RLGS

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Identification of an epigenetically silenced gene, RFX1, in human glioma cells using restriction landmark genomic scanning. / Ohashi, Yohei; Ueda, Masakazu; Kawase, Takeshi; Kawakami, Yutaka; Toda, Masahiro.

In: Oncogene, Vol. 23, No. 47, 14.10.2004, p. 7772-7779.

Research output: Contribution to journalArticle

Ohashi, Yohei ; Ueda, Masakazu ; Kawase, Takeshi ; Kawakami, Yutaka ; Toda, Masahiro. / Identification of an epigenetically silenced gene, RFX1, in human glioma cells using restriction landmark genomic scanning. In: Oncogene. 2004 ; Vol. 23, No. 47. pp. 7772-7779.
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