Gene–environment interactions

Discrete time-limited pulses of neural gene expression in response to immediate experiences are called the genomic action potential (the gAP).² The gAP affects the proteins, RNA, and chromatin structure in the cells of the nervous system, thus influencing how the cells will respond to a subsequent activation event, and how they will communicate.² The gAP plays a key role in responding to stress through recording stressful associations and shaping future responses to similar circumstances.²

An exposure to stress is associated with the stress-driven activation of the hypothalamo-pituitary-adrenal axis and the release of glucocorticoids, which trigger rapid transcriptomic responses through intracellular receptors acting as transcription factors.² The activation of transcription factors triggers downstream gene regulation starting within 30–60 minutes following the stress exposure, and peaking 3–6 hours afterwards.² Glucocorticoids elicit graded transcriptional responses depending on timing and place.² Apart from inducing a stress transcriptome profile, the glucocorticoid receptor activation also induces local epigenetic changes at the glucocorticoid response elements, its DNA binding sites.² Depending on the developmental timing and genetic factors, these epigenetic changes can be lasting, changing the subsequent stress gAP and resulting in an enhanced transcriptional response to stressful experiences,² and in changes to the expression of multiple genes involved in the stress response, immune function and metabolism.¹

References:

1. Klengel T, Binder EB. Epigenetics of stress-related psychiatric disorders and gene × environment interactions. Neuron 2015; 86 (6): 1343–1357.
2. Clayton DF, Anreiter I, Aristizabal M, et al. The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential. PNAS 2020; 117 (38): 23252–23260.