Figure 2. Experience triggered, systemic epigenetic alterations anticipates response to future signals. A model for epigenetic programming by early life stress. Perinatal stress perceived by the brain triggers release of glucocorticoids (GC) from the 
adrenal in the mother prenatally or the newborn postnatally. GC activate nuclear glucocorticoid receptors across the body, which epigenetically program (demethylate) genes that are targets of GR in brain and white blood cells (WBC). The demethylation events are insufficient for activation of these genes. A-brain specific factor (TF) is required for expression and will activate low expression of the gene in the brain but not in blood. During adulthood a stressful event transiently triggers 
a very high level of expression of the GR regulated gene specifically in the brain. Horizontal arrow, transcription; circles, 
CpG sites; CH3 in circles, methylated sites; empty circles, unmethylated CpG sites; horizonal curved lines, mRNA.