Shinji Maegawa and Hirotaka Yoshioka contributed equally to this work.
Epigenetic silencing of PEG3 gene expression in human glioma cell lines*
Article first published online: 15 MAY 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 31, Issue 1, pages 1–9, May 2001
How to Cite
Maegawa, S., Yoshioka, H., Itaba, N., Kubota, N., Nishihara, S., Shirayoshi, Y., Nanba, E. and Oshimura, M. (2001), Epigenetic silencing of PEG3 gene expression in human glioma cell lines. Mol. Carcinog., 31: 1–9. doi: 10.1002/mc.1034
- Issue published online: 1 JUN 2001
- Article first published online: 15 MAY 2001
- Manuscript Accepted: 6 MAR 2001
- Manuscript Revised: 27 FEB 2001
- Manuscript Received: 2 JAN 2001
- genomic imprinting;
- CpG island;
Genomic imprinting, the phenomenon in which alleles of genes are expressed differentially depending on their parental origins, has important consequences for mammalian development, and disturbance of normal imprinting leads to abnormal embryogenesis and some inherited diseases and is also associated with various cancers. In the context of screening for novel imprinted genes on human chromosome 19q13.4 with mouse A9 hybrids, we identified a maternal allele–specific methylated CpG island in exon 1 of paternally expressed imprinted gene 3 (PEG3), a gene that exhibits paternal allele–specific expression. Because PEG3 expression is downregulated in some gliomas and glioma cell lines, despite high-level expression in normal brain tissues, we investigated whether the loss of PEG3 expression is related to epigenetic modifications involving DNA methylation. We found monoallelic expression of PEG3 in all normal brain tissues examined and five of nine glioma cell lines that had both unmethylated and methylated alleles; the remaining four glioma cell lines exhibited gain of imprinting with hypermethylated alleles. In addition, treatment of glioma cell lines with the DNA demethylating agent 5-aza-2′-deoxycytidine reversed the silencing of PEG3 biallelically. In this article, we report that the epigenetic silencing of PEG3 expression in glioma cell lines depends on aberrant DNA methylation of an exonic CpG island, suggesting that PEG3 contributes to glioma carcinogenesis in certain cases. © 2001 Wiley-Liss, Inc.