5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels

We recently identified a class of neuronal gene inheriting high levels of intragenic methylation from the mother and maintaining this through later development. We show here that these genes are implicated in basic neuronal functions such as post-synaptic signalling, rather than neuronal development and inherit high levels of 5mC, but not 5hmC, from the mother. 5mC is distributed across the gene body and appears to facilitate transcription, as transcription is reduced in DNA methyltransferase I (Dnmt1) knockout embryonic stem cells as well as in fibroblasts treated with a methyltransferase inhibitor. However in adult brain, transcription is more closely associated with a gain in 5hmC, which occurs without a measurable loss of 5mC. These findings add to growing evidence that there may be a role for 5mC in promoting transcription as well as its classical role in gene silencing. Further interrogation of the mechanisms behind the persistence of gametic marks could potentially lead to insights into neurological disorders.