When it comes to knowledge about DNA methylation sites in the human genome, there’s no such thing as too much information. That’s why researchers in Germany have mapped DNA methylation sites on chromosome 21 in exquisite detail?with single base pair and single allele resolution. Their results are reported in the March 27, 2009 issue of PLoS Genetics.
The Herculean effort of bisulfite conversion, subcloning, and Sanger sequencing of 190 promoter regions in five human cell types focused on the smallest human chromosome, chromosome 21, which is associated with Down syndrome. A total of 580,427 CpG sites in 28,626 subclones were analyzed for methylation status. Highly methylated and unmethylated sequences were enriched, which indicated that DNA methylation functions in a switch-like manner. As expected, DNA promoter methylation strongly correlated with gene silencing.
The researchers observed differences in DNA methylation among different cell types, whereas cells from the same tissue showed similar methylation patterns. Interestingly, amplicons from different regions of the same CpG island often showed different patterns of methylation. Methylated CpGs were more likely to be surrounded by A/T-rich sequences than by G/C-rich sequences. Three genes on chromosome 21 showed allele-specific DNA methylation in leukocytes, but not in the other examined tissues. These results reveal new insights into DNA methylation patterns and effects in human cells. Check out all the details at PLoS Genetics, March 2009.