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Abstract

Covalent chemical modifications, including the acetylation of core histone proteins and methylation of cytosine in or near promoter regions of DNA, influence the efficiency with which genes are transcribed. Chemical modifications that regulate gene expression within postmitotic differentiated neurons can reflect environmental influences, including exposure to stress. These chemical modifications or “marks” may reflect downstream consequences of the transduction of extracellular chemical messengers, such as neurotransmitters, growth factors and hormones, by receptors located at the surface of the neuron or within the cell itself. The ability to decipher the epigenetic code may serve as a record of early childhood adversity that sensitizes to additional epigenetic changes caused by traumatic exposures in adulthood. Further, epigenetic therapeutic interventions may be possible that would attenuate the severity of adverse consequences associated with traumatic exposures in the child and adult. Ideally, targeted epigenetic therapeutic interventions would address stress-induced dysregulation of the hypothalamic-pituitary-adrenal axis and promote expression of therapeutically beneficial neuroplasticity factors.

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