In “Epigenetics: A new methyl mark on messengers” Anna M. Kietrys & Eric T. Kool describe a particular methylation step that used to be thought of as damage. This is the latest front in epigenetic changes.

We have studied methylation of histone proteins for some time, and recognizing that this type of modification is a form of regulation. This regulation can modify gene expression in a way that can be passed on to daughter cells and even inherited from one generation to the next.

As the change does not alter the sequence of the genome, but rather the expression properties of genes encoded by the genome, this class of modifications was described as epigenetic. For a deeper history see “A Brief History of Epigenetics” by Gary Felsenfeld from CSHL Press (perhaps not so brief).

The newly described N1-methyladenosine (m1A) methylation may well mark a mRNA for differential expression. The mechanics of this may occur at the level of splicing, wherein these marked pre-mRNAs are spliced more rapidly or efficiently. Speeding them to the cytoplasm quickly and increasing translational accessibility, thus increasing protein levels.

The m1a methylation patterns may also play a part in the regulation, in human and mouse, site preference could be found, while this was less pronounced in yeast. Finally, there is still the problem of which M1A methylations are damage, and which are true signals? The “epitranscriptome” (love the term) may just be coming into focus as a new form of epigenetic regulation.