Christmas has come and gone, but the ENCODE Project is the gift that keeps on giving. Using samples and data from ENCODE (in combo with their own data), researchers have come up with a single-base resolution map of DNA methylation across 82 human cell lines and tissues, including many cancers. With the ever increasing DNA methylation data becoming available, it won’t be long before turn by turn navigation will be standard.
The team (from Alabama, California, Washington, and N.C.) optimized reduced representation bisulfite sequencing (a.k.a., RRBS) for large-scale studies. Then, they did this on samples from the massive ENCODE Project. They combined all their data with those from ENCODE to discover lots of cool things about methylation and gene expression. They describe it as an atlas of DNA methylation. Here’s some of what they learned:
- CpGs were hypermethylated across the genome in the cancer cell lines, consistent with previous reports linking hypermethylation and cancer.
- In cancer cells, they found hypermethylation at NANOG loci that are active in embryonic stem cells, suggesting that stem cell-type activity contributes to cancer.
- Hypomethylated CpGs in cancer cluster in large regions with very few genes near telomeres and centromeres.
- The researchers reported cell-type specific methylation in noncancer samples.
- Interestingly, some methylation differences were specific to cells that were grown in culture versus primary cell lines from tissue samples—meaning scientists should be cautious when studying cultured cells.
- As expected, methylated CpGs near promoters typically meant low gene expression; methylated nonisland CpGs in gene bodies meant lots of expression. But—surprise—island CpGs in gene bodies could go either way, depending on whether they were in enhancers.
- Finally, they found non-CpG methylation in embryonic stem cells (at CAGs) and, unexpectedly, in adult human brain tissue (at CACs).
Unwrap all the info at Genome Research, January 2013.