The mechanisms responsible for this coordinated epigenomic response and its maintenance into adulthood are unknown. We observed a broad epigenomic response associated with an extensive difference in gene expression. These broad epigenomic and transcriptome changes occurred not in response to disease (e.g. cancer) [34] or artificial interventions (e.g., gene knock-out or exposure to toxins), but in the context of a natural variation in maternal behavior. Although the changes are broad, not all genes are affected. The specificity of the response and its pattern are consistent with the hypothesis that the epigenetic response is indeed a biological signal. Our data suggest that epigenetic variations in the context of early life environment variations and perhaps other environmental influences involve coordinate changes in gene-networks rather than dramatic changes in a single or few genes. Our data also suggest that this response may involve more than protein coding mRNAs. Our traditional approaches to examine relationships between epigenetic regulation, gene function and phenotype were developed to examine changes within genetic elements defined apriori (promoters, exons, 3′ gene ends) in single or few candidate genes. If,
