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 language | English |
|---|---|
| Pages (from-to) | 7772-7779 |
| Number of pages | 8 |
| Journal | Oncogene |
| Volume | 23 |
| Issue number | 47 |
| DOIs | |
| Publication status | Published - 2004 Oct 14 |
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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 journal › Article
}
TY - JOUR
T1 - Identification of an epigenetically silenced gene, RFX1, in human glioma cells using restriction landmark genomic scanning
AU - Ohashi, Yohei
AU - Ueda, Masakazu
AU - Kawase, Takeshi
AU - Kawakami, Yutaka
AU - Toda, Masahiro
PY - 2004/10/14
Y1 - 2004/10/14
N2 - 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.
AB - 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.
KW - Epigenetics
KW - Glioma
KW - Methylation
KW - RFX1
KW - RLGS
UR - http://www.scopus.com/inward/record.url?scp=7644240328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7644240328&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208058
DO - 10.1038/sj.onc.1208058
M3 - Article
C2 - 15334059
AN - SCOPUS:7644240328
VL - 23
SP - 7772
EP - 7779
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 47
ER -