title: Transcriptional control of the HERV-H LTR element of the GSDML gene in human tissues and cancer cells.
abstract: 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.
authors.affiliation: Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Sin
authors.forename: J-W
authors.initials: JW
authors.lastname: Huh
authors.forename: D-S
authors.initials: DS
authors.lastname: Kim
authors.forename: D W
authors.initials: DW
authors.lastname: Kang
authors.forename: D S
authors.initials: DS
authors.lastname: Min
authors.forename: T-H
authors.initials: TH
authors.lastname: Kim
authors.forename: H-S
authors.initials: HS
authors.lastname: Ha
authors.forename: H-H
authors.initials: HH
authors.lastname: Kim
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D002522:Chlorocebus aethiops; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000235:genetics; D048348:Reverse Transcription; D013270:Stomach; D020079:Terminal Repeat Sequences / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics; D000094524:Gasdermins
chemical_list: D009363:Neoplasm Proteins; D012313:RNA; C485887:GSDMA protein, human; D000094524:Gasdermins