The role of TET proteins in stress-induced neuroepigenetic and behavioural adaptations.

ABSTRACT

Over the past decade, critical, non-redundant roles of the ten-eleven translocation (TET) family of dioxygenase enzymes have been identified in the brain during developmental and postnatal stages. Specifically, TET-mediated active demethylation, involving the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine and subsequent oxidative derivatives, is dynamically regulated in response to environmental stimuli such as neuronal activity, learning and memory processes, and stressor exposure. Such changes may therefore perpetuate stable and dynamic transcriptional patterns within neuronal populations required for neuroplasticity and behavioural adaptation. In this review, we will highlight recent evidence supporting a role of TET protein function and active demethylation in stress-induced neuroepigenetic and behavioural adaptations. We further explore potential mechanisms by which TET proteins may mediate both the basal and pathological embedding of stressful life experiences within the brain of relevance to stress-related psychiatric disorders.