Identification of epigenetic modulators in human breast cancer by integrated analysis of DNA methylation and RNA-Seq data

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Abstract

Human tumors undergo massive changes in DNA methylation. Recent studies showed that site-specific methylation of CpG sites is determined by the DNA sequence context surrounding the CpG site, which alludes to a possible mechanism for site-specific aberrant DNA methylation in cancer through DNA-binding proteins. In this paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues in the database of The Cancer Genome Atlas (TCGA) were integrated with information of DNA motifs in seven databases to find DNA-binding proteins and their binding motifs that were involved in aberrant DNA methylation in breast cancer. A total of 42,850 differentially methylated regions (DMRs) that include 77,298 CpG sites were detected in breast cancer. One hundred eight DNA motifs were found to be enriched in DMRs, and 109 genes encoding proteins binding to these motifs were determined. Based on these motifs and genes, 63 methylation modulator genes were identified to regulate differentially methylated CpG sites in breast cancer. A network of these 63 modulator genes and 645 transcription factors was constructed, and 20 network modules were determined. A number of pathways and gene sets related to breast cancer were found to be enriched in these network modules. The 63 methylation modulator genes identified may play an important role in aberrant methylation of CpG sites in breast cancer. They may help to understand site-specific dysregulation of DNA methylation and provide epigenetic markers for breast cancer.

Original languageEnglish (US)
JournalEpigenetics
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

DNA Methylation
Epigenomics
RNA
Breast Neoplasms
Methylation
Nucleotide Motifs
Genes
DNA-Binding Proteins
Protein Binding
Databases
Neoplasms
Atlases
Transcription Factors
Genome
Proteins

Keywords

  • breast cancer
  • DNA methylation
  • DNA motif
  • DNA-binding protein
  • epigenetic modulator
  • gene network

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

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title = "Identification of epigenetic modulators in human breast cancer by integrated analysis of DNA methylation and RNA-Seq data",
abstract = "Human tumors undergo massive changes in DNA methylation. Recent studies showed that site-specific methylation of CpG sites is determined by the DNA sequence context surrounding the CpG site, which alludes to a possible mechanism for site-specific aberrant DNA methylation in cancer through DNA-binding proteins. In this paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues in the database of The Cancer Genome Atlas (TCGA) were integrated with information of DNA motifs in seven databases to find DNA-binding proteins and their binding motifs that were involved in aberrant DNA methylation in breast cancer. A total of 42,850 differentially methylated regions (DMRs) that include 77,298 CpG sites were detected in breast cancer. One hundred eight DNA motifs were found to be enriched in DMRs, and 109 genes encoding proteins binding to these motifs were determined. Based on these motifs and genes, 63 methylation modulator genes were identified to regulate differentially methylated CpG sites in breast cancer. A network of these 63 modulator genes and 645 transcription factors was constructed, and 20 network modules were determined. A number of pathways and gene sets related to breast cancer were found to be enriched in these network modules. The 63 methylation modulator genes identified may play an important role in aberrant methylation of CpG sites in breast cancer. They may help to understand site-specific dysregulation of DNA methylation and provide epigenetic markers for breast cancer.",
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author = "Xin Zhou and Zhibin Chen and Xiaodong Cai",
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AB - Human tumors undergo massive changes in DNA methylation. Recent studies showed that site-specific methylation of CpG sites is determined by the DNA sequence context surrounding the CpG site, which alludes to a possible mechanism for site-specific aberrant DNA methylation in cancer through DNA-binding proteins. In this paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues in the database of The Cancer Genome Atlas (TCGA) were integrated with information of DNA motifs in seven databases to find DNA-binding proteins and their binding motifs that were involved in aberrant DNA methylation in breast cancer. A total of 42,850 differentially methylated regions (DMRs) that include 77,298 CpG sites were detected in breast cancer. One hundred eight DNA motifs were found to be enriched in DMRs, and 109 genes encoding proteins binding to these motifs were determined. Based on these motifs and genes, 63 methylation modulator genes were identified to regulate differentially methylated CpG sites in breast cancer. A network of these 63 modulator genes and 645 transcription factors was constructed, and 20 network modules were determined. A number of pathways and gene sets related to breast cancer were found to be enriched in these network modules. The 63 methylation modulator genes identified may play an important role in aberrant methylation of CpG sites in breast cancer. They may help to understand site-specific dysregulation of DNA methylation and provide epigenetic markers for breast cancer.

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