The journal Epigenetics & Chromatin just put out two interesting new papers about the epigenetics of FASD. The first is by Veazey et al. They found significant alterations to histone mods (H3K9me2, H3K9ac, and H3K27me3) at days 7 and 17 that are dose dependent and correlate to severity of phenotype. They also found changes to homeobox and histone genes, two things we saw in our own earlier mouse model but had not pursued. They also noticed that in this model, the profiles were different after a 4 day recovery period, something we’ve also seen when examining the short and long term transcriptional changes across a wider window but have not examined at the epigenetic level. Another similarity was that the chromatin mods don’t usually line up with current transcription, which is also in line with our developmental footprint idea. This observation was also complemented by finding altered transcription in a number of epigenetic writers. I also imagine some of the differences between models here relate to stem cell models and ontogeny.
The second paper is by Zhang et al. and deals with the discovery of a glutamate transporter that shows age and sex dependent alterations to expression. The transcriptional increase appears to be driven by decreased DNA methylation and an increase in activating H3K4me3. Also of interest was that while the mRNA levels were increased the protein levels were decreased, which appears to be an increase in an imprinted miRNA, from a cluster we’ve previously identified, which was functionally confirmed to bind. Interestingly, there was also a correlation between this miRNA in the brain and levels of it in the serum. While it is a mouse specific cluster, it hints that the other clusters shared with humans may leave the same clues.
In terms of caveats, both papers have a bit of a bias in that they were not scanning the genome but rather pre-picked players, but that is also just my omic bias talking. Overall, these papers continue to provide evidence for the consensus idea that FASD is in part maintained by an initial alteration combined with recovery response that may one day be narrowed down to certain drivers of phenotype. The targets arising from these groups, and our own, would make excellent candidates for epigenome editing, which we just published a review on in the very same journal.