Between reading Dilbert cartoons and refilling their Swingline staplers, many of corporate America’s finest day dream of holidays to distant islands, but they’re not alone. Researchers studying DNA methylation have made minimal attempts to hide their infatuation with CpG islands, after all, these regions tend to associate themselves with prestigious protein-coding regions of genes.
An ultra-talented crew from Johns Hopkins used comprehensive high-throughput array-based relative methylation (CHARM) analysis to get up close with the methylation status in various tissues, including colorectal cancer and shook up some of the long held ideas of the what/where/when of DNA methylation in tissue and disease in the January 18th issue of Nature Genetics.
Some of the unexpected results, that shift attention away from CpG islands over to CpG island “shores,” methylation hotspots that lie on the outskirts of CpG islands, include:
1. Over 16,000 regions of tissue differential methylation regions which they dubbed “T-DMRs”
2. The majority of the T-DMRs were found within 2 kb of the CpG island “shores,” methylation hotspots that lie on the outskirts of CpG islands,
3. Almost 3,000 regions of cancer-specific differential methylation regions which they dubbed C-DMRs
This paper was packed with good stuff, but some of the highlights included:
1. The majority of DNA methylation variation occurred far more frequently in CpG island “shores” rather than CpG islands
2. The regions were highly conserved between human and mouse models
3. Most of the cancer related variation in the regions (C-DMRs) overlapped with the tissue-specific regions (T-DMRs) and these mapped frequently to CpG island “shores.”
4. The DMRs (cancer and tissue-specific) frequently associate with alternative transcriptional start sites suggesting a potential role in regulating alternative transcription
We never feature a paper we don’t think is cool, but this one is definitely one of our favorites. You’ll definitely want to check out all of the details yourself in Nature Genetics, February 2009.