DNA Methylation Profiling of the Human Major Histocompatibility Complex: A Pilot Study for the Human Epigenome Project
Figure 8
Comparison of DNA Methylation with Gene Expression
Amplicons generated from prostate (yellow), lung (blue), and liver (green) samples were divided into two categories: “upstream” and “intragenic”. The median methylation values for the amplicons were calculated as described in the text, and these were then classified as hypomethylated (median methylation less than 50%) or hypermethylated (median methylation greater than 50%), and plotted against the cDNA microarray expression data available at http://expression.gnf.org (Su et al. 2002). The expression values are expressed as average difference values (ADVs) for each gene. The average difference value is computed using Affymetrix software and is proportional to mRNA content in the sample, with a value of 200 being a conservative cut-off below which a gene can be classified as being not expressed. The average difference values are the mean of 2 or 3 independent experiments. For prostate and liver, the expression levels associated with the hypermethylated upstream amplicons were significantly lower than the expression levels associated with the hypomethylated upstream amplicons (p < 0.0001 for prostate and p < 0.01 for liver). For lung, there was no significant difference between the expression levels associated with the hypermethylated upstream amplicons and those of the hypomethylated upstream amplicons (p > 0.3). There was no correlation between expression and methylation for the intragenic amplicons for any of the three tissues (p > 0.3). The width of the bars is indicative of the number of amplicons in each category: prostate upstream, hypermethylated (n = 9); prostate upstream, hypomethylated (n = 15); prostate intragenic, hypermethylated (n = 109); prostate intragenic, hypomethylated (n = 53); liver upstream, hypermethylated (n = 9); liver upstream, hypomethylated (n = 14); liver intragenic, hypermethylated (n = 115); liver intragenic, hypomethylated (n = 45); lung upstream, hypermethylated (n = 9); lung upstream, hypomethylated (n = 13); lung intragenic, hypermethylated (n = 112); and lung intragenic, hypomethylated (n = 57).