The novel human endogenous retrovirus-related gene, psiTPTE22-HERV, is silenced by DNA methylation in cancers

✍ Scribed by Qiaoyi Liang; Jiayi Ding; Rongzhen Xu; Zefeng Xu; Shu Zheng

• Book ID: 102864040
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: French
• Weight: 933 KB
• Volume: 127
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.25213

✦ Synopsis

Abstract

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 RT‐PCR 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.