Coordinate downregulation of a novel imprinted transcript ITUP1 with PEG3 in glioma cell lines.
The human paternally expressed gene 3 (PEG3) on chromosome 19q13.4 is one of the candidate tumor suppressor genes for glioma. We have previously reported that the epigenetic silencing of PEG3 expression in glioma cell lines is dependent on aberrant DNA methylation of an exonic CpG island. Here, we have identified three expressed sequence tags (ESTs), H80201, H78825 and AW197312, that exhibit paternal allele-specific expression, using human monochromosomal hybrids containing the paternal or maternal origin of PEG3 locus. The EST H80201 was shown to be expressed only from the paternal allele in normal human lymphoblasts by utilizing a single nucleotide polymorphism (SNP). Monoallelic expression of EST H80201 was also detected in non-tumor adult human brain tissues of gliomas. These ESTs were located directly adjacent to PEG3 in a head-to-head orientation. We have named this new transcript, imprinted transcript 1, which is located upstream but oppositely oriented to PEG3 (ITUP1). The ITUP1 showed a similar expression profile with PEG3 in glioma cell lines. Bisulfite genomic sequencing and reverse transcription (RT)-PCR analysis indicated that hypermethylation of the promoter region correlated with the absence of these transcripts. This suggests that ITUP1 and PEG3 are coordinately regulated, and that downregulation of the both genes may be important in the development of glioma.
Maegawa
Shinji
S
Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, 86 Nishimachi, Yonago City, Tottori 683-8503, Japan.
Itaba
Noriko
N
Otsuka
Susumu
S
Kamitani
Hideki
H
Watanabe
Takashi
T
Tahimic
Candice G T
CG
Nanba
Eiji
E
Oshimura
Mitsuo
M
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D020224:Expressed Sequence Tags; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; C097901:Peg3 protein, mouse; D014157:Transcription Factors; D011494:Protein Kinases