Identification of genes with consistent methylation levels across different human tissues

Sci Rep. 2014 Mar 12:4:4351. doi: 10.1038/srep04351.

Abstract

DNA methylation plays an important role in regulating cell growth and disease development. Methylation profiles are examined by bisulfite conversion; however, the lack of markers for bisulfite conversion efficiency and appropriate internal control genes remains a major challenge. To address these issues, we utilized two bioinformatics approaches, coefficients of variances and resampling tests, to identify probes showing stable methylation levels from several independent microarray datasets. Mass spectrometry validated the consistently high methylation levels of the five probes (N4BP2, EGFL8, CTRB1, TSPAN3, and ZNF690) in 13 human tissue types from 24 cell lines. Linear associations between detected methylation levels and methyl concentrations of DNA samples were further demonstrated in three genes (N4BP2, EGFL8, and CTRB1). To summarize, we identified five genes which may serve as internal controls for methylation studies by analyzing large-scale microarray data, and three of them can be used as markers for evaluating the efficiency of bisulfite conversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers / metabolism
  • Calcium-Binding Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Chymotrypsin / genetics
  • Chymotrypsin / metabolism*
  • Computational Biology*
  • DNA Methylation
  • DNA Repair Enzymes
  • EGF Family of Proteins
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Humans
  • Mass Spectrometry
  • Oligonucleotide Array Sequence Analysis
  • Protein Processing, Post-Translational*
  • Reference Standards
  • Tetraspanins / genetics
  • Tetraspanins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Calcium-Binding Proteins
  • Carrier Proteins
  • EGF Family of Proteins
  • EGFL8 protein, human
  • Endothelial Growth Factors
  • N4BP2 protein, human
  • Tetraspanins
  • Chymotrypsin
  • chymotrypsin B
  • DNA Repair Enzymes