Genome-wide DNA methylation analysis reveals estrogen-mediated epigenetic repression of metallothionein-1 gene cluster in breast cancer

Clinical Epigenetics
Rohit R JadhavVictor X Jin

Abstract

Recent genome-wide analysis has shown that DNA methylation spans long stretches of chromosome regions consisting of clusters of contiguous CpG islands or gene families. Hypermethylation of various gene clusters has been reported in many types of cancer. In this study, we conducted methyl-binding domain capture (MBDCap) sequencing (MBD-seq) analysis on a breast cancer cohort consisting of 77 patients and 10 normal controls, as well as a panel of 38 breast cancer cell lines. Bioinformatics analysis determined seven gene clusters with a significant difference in overall survival (OS) and further revealed a distinct feature that the conservation of a large gene cluster (approximately 70 kb) metallothionein-1 (MT1) among 45 species is much lower than the average of all RefSeq genes. Furthermore, we found that DNA methylation is an important epigenetic regulator contributing to gene repression of MT1 gene cluster in both ERα positive (ERα+) and ERα negative (ERα-) breast tumors. In silico analysis revealed much lower gene expression of this cluster in The Cancer Genome Atlas (TCGA) cohort for ERα + tumors. To further investigate the role of estrogen, we conducted 17β-estradiol (E2) and demethylating agent 5-aza-2'-deoxycytidine (DAC)...Continue Reading

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Citations

Feb 26, 2016·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Jana Elena KesselsPeter Uciechowski
Sep 22, 2016·Cell Biochemistry and Function·Xiaogang DongWenjia Guo
Nov 13, 2015·Cancers·John Verigos, Angeliki Magklara
Apr 2, 2019·Scientific Reports·Bernadeta MasiulionytėDaina Skiriutė
Aug 14, 2018·Molecular Cancer·Chuchu ShaoHua Shen
Jul 21, 2016·Briefings in Bioinformatics·Xiaofei YangShihua Zhang
Jun 12, 2018·Frontiers in Neuroscience·Matthew C S DenleyDeepak P Srivastava
Dec 23, 2016·Statistics in Biosciences·Zhaohui QinShili Lin

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Methods Mentioned

BETA
RNA-seq
MDB-seq
MBD-seq
reverse transcription PCR
PCR
Assay

Software Mentioned

pROC package of R
R
Illumina
Image J
Python

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