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This Gene \u00d7 Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid release upon exposure to stress. Both endophenotypes are regulated by the neuropeptide corticotropin-releasing factor (CRF) or hormone, which is expressed by the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central amygdala (CeA). Therefore, we hypothesized that altered regulation of the expression of CRF in these areas represents a major neurobiological mechanism underlying the interaction of early life stress and<jats:italic>5-HTT<\/jats:italic>gene variation. The programming of gene transcription by Gene \u00d7 Environment interactions has been proposed to involve epigenetic mechanisms such as DNA methylation. In this study, we report that early life stress and<jats:italic>5-HTT<\/jats:italic>genotype interact to affect DNA methylation of the<jats:italic>Crf<\/jats:italic>gene promoter in the CeA of adult male rats. Furthermore, we found that DNA methylation of a specific site in the<jats:italic>Crf<\/jats:italic>promoter significantly correlated with CRF mRNA levels in the CeA. Moreover, CeA CRF mRNA levels correlated with stress coping behavior in a learned helplessness paradigm. Together, our findings warrant further investigation of the link of<jats:italic>Crf<\/jats:italic>promoter methylation and CRF expression in the CeA with behavioral changes that are relevant for psychopathology.<\/jats:p>","DOI":"10.1017\/s0954579414001345","type":"journal-article","created":{"date-parts":[[2015,2,2]],"date-time":"2015-02-02T09:32:12Z","timestamp":1422869532000},"page":"123-135","source":"Crossref","is-referenced-by-count":52,"title":["Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain"],"prefix":"10.1017","volume":"27","author":[{"given":"Rick H. 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