Sin H-S, Huh J-W, Kim D-S, Kang D W, Min D S, Kim T-H, Ha H-S, Kim H-H, Lee S-Y, Kim H-S
Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Korea.
Arch Virol. 2006 Oct;151(10):1985-94. doi: 10.1007/s00705-006-0764-5. Epub 2006 Apr 20.
Long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) have been reported to serve as alternative promoters in functional genes. The GSDML (gasdermin-like protein) gene located on human chromosome 17q21 has been found to be an oncogenomic recombination hotspot. Here, we identified the LTR element of HERV-H with reverse orientation as an alternative promoter of the GSDML gene and analyzed its expression pattern in human tissues and cancer cells. A reporter gene assay of the promoter activity of the LTR on the GSDML gene in human cancer cell lines (HCT-116 and HeLa) and a kidney cell line (Cos7) of African green monkey indicated that the LTR promoter with reverse orientation had stronger promoter activity than forward one. The transcripts of this LTR-derived promoter were widely distributed in various human tissues and cancer cells, whereas the transcripts of the cellular promoter were found only in stomach tissues and some cancer cells (HCT116, MCF7, U937, C-33A, and PC3). These findings suggest that the LTR element on the GSDML gene was integrated into the hominoid lineage and acquired the role of transcriptional regulation of human tissues and cancer cells.
据报道，人类内源性逆转录病毒（HERV）的长末端重复序列（LTR）可作为功能基因中的替代启动子。位于人类17号染色体q21上的GSDML（gasdermin样蛋白）基因已被发现是一个肿瘤基因组重组热点。在此，我们鉴定出反向的HERV-H的LTR元件作为GSDML基因的替代启动子，并分析了其在人体组织和癌细胞中的表达模式。对人癌细胞系（HCT-116和HeLa）以及非洲绿猴肾细胞系（Cos7）中GSDML基因上LTR启动子活性的报告基因检测表明，反向的LTR启动子比正向启动子具有更强的启动子活性。该LTR衍生启动子的转录本广泛分布于各种人体组织和癌细胞中，而细胞启动子的转录本仅在胃组织和一些癌细胞（HCT116、MCF7、U937、C-33A和PC3）中发现。这些发现表明，GSDML基因上的LTR元件已整合到类人猿谱系中，并获得了对人体组织和癌细胞进行转录调控的作用。
