title: Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells.
abstract: CpG methylation of DNA takes part in a specific epigenetic memory that plays crucial roles in the differentiation and abnormality of the cells. The methylation pattern aberration of genomes is affected in three ways, namely DNA methyltransferase (DNMT), ten-eleven translocation (TET), and methyl-binding domain (MBD) proteins. Of these, TET enzymes have recently been demonstrated to be master modifier enzymes in the DNA methylation process. Additionally, recent studies emphasize that not only epigenetic phenomena play a role in controlling hypoxia pathway, but the hypoxia condition also triggers hypomethylation of genomes that may help with the expression of hypoxia pathway genes. In this study, we suggested that TET1 and TET2 could play a role in the demethylation of genomes under chemical hypoxia conditions. Herein, the evaluating methylation status and mRNA expression of mentioned genes were utilized through real-time PCR and methylation-specific PCR (MSP), respectively. Our results showed that TET1 and TET2 genes were overexpressed (P < 0.05) under chemical hypoxia conditions in Retinal Pigment Epithelial (RPE) cells, whereas the promoter methylation status of them were hypomethylated in the same condition. Therefore, chemical hypoxia not only causes overexpression of TET1 and TET2 but also could gradually do promoter demethylation of same genes. This is the first study to show the relationship between epigenetics and the expression of mentioned genes related to hypoxia pathways. Furthermore, it seems that these associations in RPE cells are subjected to chemical hypoxia as a mechanism that could play a crucial role in methylation pattern changes of hypoxia-related diseases such as cancer and ischemia. J. Cell. Biochem. 118: 3193-3204, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Reza
authors.identifier: 0000-0002-5847-3594
authors.initials: MR
authors.lastname: Alivand
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Zahra-Soheila
authors.initials: ZS
authors.lastname: Soheili
authors.affiliation: Medical Laser Research Center, ACECR, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Pornour
authors.affiliation: Department of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Solali
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Sabouni
mesh_terms: D015687:Cell Hypoxia; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D049308:Dioxygenases; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: DNA METHYLATION; HIF1α, -2; HYPOXIA; HYPOXIA INDUCIBLE FACTOR1 ALPHA,-2; METHYLATION SPECIFIC PCR; MSP; REAL-TIME PCR; TEN-ELEVEN TRANSLOCATION; TET