The role of TET proteins in stress

The ten-eleven translocation (TET) family of dioxygenase enzymes has been discovered to play crucial, non-redundant roles in the brain during developmental and postnatal phases over the last decade. TET-mediated active demethylation, which involves 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, to name a few examples. As a result, such alterations may help to maintain the stable and dynamic transcriptional patterns essential for neuroplasticity and behavioural adaptability within neuronal populations. We will emphasise recent evidence that suggests TET protein function and active demethylation play a role in stress-induced neuroepigenetic and behavioural adaptations in this review. We also look at how TET proteins might mediate both the physiological and pathological embedding of stressful life experiences in the brain, which is relevant to stress-related mental diseases.