The novel human endogenous retrovirus-related gene, psiTPTE22-HERV, is silenced by DNA methylation in cancers
The novel human endogenous retrovirus-related gene, psiTPTE22-HERV, is silenced by DNA methylation in cancers
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DOI：
10.1002/ijc.25213
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发表时间：
2010-10-15
影响因子：
6.4
通讯作者：
Zheng, Shu
中科院分区：
文献类型：
--
作者：
Liang, Qiaoyi;Ding, Jiayi;Zheng, Shu
psiTPTE 22基因已被指定为TPTE假基因。我们的研究发现，psiTPTE 22的5'部分与TPTE没有序列相似性，并且含有3.8kb的人内源性逆转录病毒（HERV）元件。由于HERV元件，psiTPTE 22的5'部分（psiTPTE 22-HERV）作为基因独立表达。人类和黑猩猩DNA序列的比较表明，psiTPTE 22-HERV是人类特异性的。我们通过基于PCR的策略从psiTPTE 22-HERV中鉴定了3种选择性剪接的转录变体，其使用HERV元件中包含的转录终止信号。在2个较长的转录本中含有一个402-nt的ORF。使用化学合成肽产生的抗体的Western印迹证实了从该ORF翻译的15-kDa蛋白质。RT-PCR结果表明，psiTPTE 22-HERV基因主要在psiTPTE 22-HERV基因的表达产物中表达。实时荧光定量RTPCR结果显示402-nt ORF在肾、肝、胃和肺等正常组织中表达上调，而在相应肿瘤组织中表达下调。该基因位于22号染色体着丝粒附近，启动子区域周围具有高GC含量。亚硫酸氢盐测序PCR结果表明，它在癌症中通过DNA甲基化沉默。psiTPTE 22-HERV的表达可以使用DNA甲基化和组蛋白脱乙酰酶抑制剂在癌细胞中恢复。这些结果表明psiTPTE 22-HERV通过DNA甲基化进行表观遗传调控。我们的研究为进一步研究一个有趣的HERV相关人类特异性基因铺平了道路，该基因在癌症中通过DNA甲基化沉默。
The psiTPTE22 gene has been designated as a TPTE pseudogene. Our study found that the 5' part of psiTPTE22 has no sequence similarity to TPTE and contains a 3.8-kb human endogenous retrovirus (HERV) element. Because of the HERV element, the 5' part of psiTPTE22 (psiTPTE22-HERV) expresses independently as a gene. Comparison between the DNA sequences of humans and chimps indicated that psiTPTE22-HERV is human specific. We identified 3 alternatively spliced transcript variants from psiTPTE22-HERV by a PCR-based strategy, which use the transcriptional termination signal contained in the HERV element. A 402-nt ORF was contained in the 2 longer transcripts. Western blotting using antibodies produced with chemically synthesized peptide confirmed that a 15-kDa protein was translated from this ORF. RT-PCR results indicated that the ORF-containing transcripts were mainly expressed in psiTPTE22-HERV-expressing samples. Real-time quantitative RTPCR results showed that expression of the 402-nt ORF was upregulated in normal tissues of kidney, liver, stomach, and lung but downregulated in corresponding tumor tissues. This gene is located near the centromere of chromosome 22 and has a high GC content around the promoter region. Bisulfite sequencing PCR results indicated that it is silenced in cancers by DNA methylation. The expression of psiTPTE22-HERV can be recovered in cancer cells using DNA methylation and histone deacetylase inhibitors. These results suggest psiTPTE22-HERV is regulated epigenetically by DNA methylation. Our study paved the way for further study on an interesting HERV-related human-specific gene, which is silenced in cancers by DNA methylation.