Dr Wei Wei, Queensland Brain Institute, The University of Queensland, Brisbane, QLD.
Epigenetic mechanisms are critically involved in regulating gene expression underlying learning and memory. Dynamic variation in DNA methylation has emerged as one of the driving factors behind experience dependent plasticity of nervous system and the formation of fear-related memory. However, the story regarding DNA methylation and neural plasticity is far from complete. It has become evident that 5-methylcytosine (5mC) can be successively oxidised and converted to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (Tet) family proteins. Levels of 5hmC, 5fC and 5caC in DNA vary between different mammalian tissues but are highest in embryonic stem cells and in the brain. In the adult brain, particularly those with non-dividing cells such as neurons, these modifications may potentially be stable and therefore serve as epigenetic signals for persistent transcriptional activity. We have recently found that, upon behavioral training, there is a dramatic redistribution of 5hmC in response to fear and fear extinction training. We have begun to extend these findings to include 5fC, which may also represent a unique epigenetic signal and/or carry regulatory function in the adult brain. Preliminary evidence indicates that inhibitor of growth family member 1 (ING1), a key 5fC reader, interacts with 5fC at the promoter region of brain-derived neurotrophic factor (BDNF) I, but not BDNF IV, which leads to activation of BDNF exon I mRNA expression. Together our data suggest that, the neuronal epigenome and DNA modifications in particular, are far more complicated and dynamically regulated than currently appreciated.