Coordinate downregulation of a novel imprinted transcript ITUP1 with PEG3 in glioma cell lines
Coordinate downregulation of a novel imprinted transcript ITUP1 with PEG3 in glioma cell lines
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DOI：
10.1093/dnares/11.1.37
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发表时间：
2004-02-29
期刊：
影响因子：
4.1
通讯作者：
Oshimura, M
中科院分区：
文献类型：
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作者：
Maegawa, S;Itaba, N;Oshimura, M
位于染色体19q13.4的人父系表达基因3（PEG 3）是胶质瘤的候选抑癌基因之一。我们以前曾报道过，胶质瘤细胞系中PEG 3表达的表观遗传沉默依赖于外显子CpG岛的异常DNA甲基化。在这里，我们已经确定了三个表达序列标签（EST），H80201，H78825和AW 197312，表现出父系等位基因特异性表达，使用人类单染色体杂交含有父系或母系来源的PEG 3基因座。EST H80201通过利用单核苷酸多态性（SNP）显示仅从正常人淋巴母细胞中的父系等位基因表达。EST H80201的单等位基因表达也在非肿瘤成人脑胶质瘤组织中检测到。这些EST以头对头的方向直接邻近PEG 3定位。我们将这种新的转录本命名为印迹转录本1，它位于PEG 3（ITUP 1）的上游，但方向相反。ITUP 1在胶质瘤细胞系中显示出与PEG 3相似的表达谱。亚硫酸氢盐基因组测序和逆转录（RT）-PCR分析表明，启动子区域的超甲基化与这些转录本的缺乏。这表明ITUP 1和PEG 3是协同调节的，并且这两个基因的下调在胶质瘤的发展中可能是重要的。
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.