The current study puts an end to that notion. The researchers found in their analysis of those modifications across the genomereferred to, collectively, as the epigenomethat master genes that govern the regulation of early embryonic development tend largely to be switched off by H3K27me3 histone methylation. Meanwhile, those that orchestrate the later stages of cellular differentiation, when cells become increasingly committed to specific functions, are primarily silenced by DNA methylation.
"You can sort of glean the logic of animal development in this difference," says Ren. "Histone methylation is relatively easy to reverse. But reversing DNA methylation is a complex process, one that requires more resources and is much more likely to result in potentially deleterious mutations. So it makes sense that histone methylation is largely used to silence master genes that may be needed at multiple points during development, while DNA methylation is mostly used to switch off genes at later stages, when cells have already been tailored to specific functions, and those genes are less likely to be needed again."
The researchers also found that the human genome is peppered with more than 1,200 large regions that are consistently devoid of DNA methylation throughout development. It turns out that many of the genes considered master regulators of development are located in these regions, which the researchers call DNA methylation valleys (DMVs). Further, the team found that the DMVs are abnormally methylated in colon cancer cells. While it has long been known that aberrant DNA methylation plays an important role in various cancers, these results suggest that changes to the cell's DNA methylation machinery itself may b
|Contact: Rachel Steinhardt|
Ludwig Institute for Cancer Research