It has generally been thought that methylation is a stable epigenetic mark and that changes in methylation are unidirectional; and further, that cells become increasingly methylated as they move through the differentiation process toward their mature identity. And in fact, the only known direction of active change is from an unmethylated state to a methylated state.
The new data suggests, however, that dynamic changes in methylation status may be possible. The relevant evidence comes from blood stem cells, which were observed to have methylation patterns that the team describes as "intermediately methylated," seemingly in dynamic equilibria of the two extreme states of "methylated" and "unmethylated."
According to Hodges, this raises the possibility that methylation might in fact be bidirectional, and that there might be an as yet undiscovered, active mechanism that performs de-methylation. No known enzyme has this ability to remove methyl groups from DNA; DNA methyltransferase is the well-known enzyme that catalyzes the addition of methyl groups.
Yet another of the team's unexpected findings concerns the position of HMRs relative to know genic regions. While unmethylated regions tend to be associated with nearby genes that are capable of being expressed, the team found, according to Hodges, "a lot of HMRs located far away from any annotated gene locus." One notable thing about these regions, she says, "is that they were highly enriched for binding sites of specific regulatory molecules that are involved in chromatin organization."
Chromatin consists of DNA and the protein complexes called histones around which genomic DNA is packed. In a given cell, chromatin organization, like methylation, helps to determine whether specific genes can be expressed or not.
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory