with Moshe Szyf, PhD
A body of epidemiological data has suggested that childhood stress is associated with a variety of physical and mental health vulnerabilities including post-traumatic stress later in life. The critical question is: what is the mechanism? How could experience early in life be registered in the genome and affect phenotypes later in life? We suggest that DNA methylation, a chemical modification of the DNA, mediates the long-term effects of early life environmental exposures. Basic principles of DNA methylation and how DNA methylation sculpts the genome during differentiation to create cell type specific identity for DNA will be discussed. It will be suggested that the same mechanism generates exposure-specific identity to DNA. The social and physical environments acting through signaling pathway target changes in DNA methylation to particular gene networks. The alterations in the state of methylation of these gene networks stably reprogram gene expression and alter the phenotype. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome “adaptation” that molecularly embeds the early experiences of a child (“nurture”) in the genome (“nature”). Data that supports this hypothesis from rodent, non-human primates, humans and population studies will be discussed. .