Post-traumatic stress disorder (PTSD) is unique among psychiatric disorders 
since there is an explicit requirement for the presence of a well-defined 
precipitating environmental event. This suggests the participation of adaptable 
molecular processes such as epigenetic modifications, including acetylation and 
methylation of histones and DNA methylation. In the present study we 
investigated whether changes in DNA methylation are associated with the effects 
of traumatic stressor, using a validated PTSD rat model. Screening of genomic 
DNA methylation patterns revealed that maladaptation to traumatic stress is 
associated with numerous changes in the methylation pattern of rat hippocampus. 
Of the differentially methylated genes revealed by this global screening, Disks 
Large-Associated Protein (Dlgap2) was of special interest, demonstrating an 
increase in a specific methylation site which was associated with a reduction in 
its gene expression in PTSD-like compared to non-PTSD-like rats. The association 
between the methylation rate and Dlgap2 expression was further substantiated by 
re-dividing the rats according to their methylation state. A significantly 
higher expression was observed in the non-methylated compared to methylated 
rats. In addition, taking all rats as one group revealed a significant 
correlation between their behavioural stress responses and Dlgap2 transcript 
levels. These results suggest that alterations in global methylation pattern are 
involved in behavioural adaptation to environmental stress and pinpoint Dlgap2 
as a possible target in PTSD.