title: Association of epigenetic alterations in the human C7orf24 gene with the aberrant gene expression in malignant cells.
abstract: Human chromosome 7 open reading frame 24 (C7orf24)/γ-glutamyl cyclotransferase has been suggested to be a potential diagnostic marker for several cancers, including carcinomas in the bladder urothelium, breast and endometrial epithelium. We here investigated the epigenetic regulation of the human C7orf24 promoter in normal diploid ARPE-19 and IMR-90 cells and in the MCF-7 and HeLa cancer cell lines to understand the transcriptional basis for the malignant-associated high expression of C7orf24. Chromatin immunoprecipitation analysis revealed that histone modifications associated with active chromatin were enriched in the proximal region but not in the distal region of the C7orf24 promoter in HeLa and MCF-7 cells. In contrast, elevated levels of histone modifications leading to transcriptional repression and accumulation of heterochromatin proteins in the C7orf24 promoter were observed in the ARPE-19 and IMR-90 cells, compared to the levels in HeLa and MCF-7 cancer cells. In parallel, the CpG island of the C7orf24 promoter was methylated to a greater extent in the normal cells than in the cancer cells. These results suggest that the transcriptional silencing of the C7orf24 gene in the non-malignant cells is elicited through heterochromatin formation in its promoter region; aberrant expression of C7orf24 associated with malignant alterations results from changes in chromatin dynamics.
authors.affiliation: Division of Bioinformatics and Chemical Genomics, Department of System Chemotherapy and Molecular Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan and Department of Clinical Oncology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ohno
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D005722:gamma-Glutamylcyclotransferase / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; C572776:GGCT protein, human; D006657:Histones; D009363:Neoplasm Proteins; D005722:gamma-Glutamylcyclotransferase
keywords: C7orf24; DNA methylation; histone modification; tumour biomarker; γ-glutamyl cyclotransferase