Faculty Collaboration Database

Novel Epigenetic Controlling of Hypoxia Pathway Related to Overexpression and Promoter Hypomethylation of TET1 and TET2 in RPE Cells. J Cell Biochem 2017 Oct;118(10):3193-3204

Date

03/03/2017

Pubmed ID

28252217

DOI

10.1002/jcb.25965

Scopus ID

2-s2.0-85017474086 (requires institutional sign-in at Scopus site)   24 Citations

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.

Author List

Alivand MR, Soheili ZS, Pornour M, Solali S, Sabouni F

Author

Mohammadreza Alivand DPhil Postdoctoral Fellow in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Hypoxia
DNA Methylation
DNA-Binding Proteins
Dioxygenases
Epigenesis, Genetic
Female
Humans
Male
Mixed Function Oxygenases
Promoter Regions, Genetic
Proto-Oncogene Proteins
Retinal Pigment Epithelium