We are interested in elucidating how the genome is connected to the environment, and how this relationship shapes brain and behaviour across the lifespan. Embedded within the chromatin landscape, directly at the interface between intracellular signaling and genomic DNA, epigenetic mechanisms including histone modifications, DNA methylation and non-coding RNA’s represent an attractive foundation for experience-dependent, long-lasting changes in gene expression, cellular function and behaviour. In contrast to the information conveyed by a static genome, the epigenome is very dynamic and can be modified by exposure to a variety of environmental stimuli including fear-related learning, exposure to drugs of abuse, environmental toxins, dietary factors, and social interaction. For example, we have recently discovered that fear-related learning is associated with epigenetic modification of genes within the prefrontal cortex. The acquisition and extinction of conditioned fear lead to distinct patterns of histone acetylation around the P4 promoter of the gene encoding brain-derived neurotrophic factor (BDNF) (Bredy et al., 2007). We have also shown that histone deacetylase (HDAC) inhibitors, when administered during spaced extinction training, enhance long-term extinction memory and prevent renewal of conditioned fear (Bredy et al., 2008), evidence which suggests that the epigenome may represent a therapeutic point of intervention for the treatment of fear-related anxiety disorders.

Epigenetics refers to all genetic information not encoded in the DNA sequence, with the best-understood consequence of epigenetic modifications being the regulation of gene expression and cellular function. Within the promoter region of genes in all cell types, post-translational modification of histone proteins (acetylation, methylation, phosphorylation, ubiquitination, and sumoylation) and covalent modification of DNA (methylation) control the accessibility of transcription factors to DNA, while non-coding RNAs (i.e. microRNA) directly regulate genes by interfering with translation, both capable of being either permissive or repressive for overall gene function. In this context, epigenetic events are defined as “structural adaptation of chromosomal regions so as to register, signal and perpetuate altered activity states” (Bird, 2007). We are exploring the hypothesis that the epigenome serves an important role as the interface between environmental signals, genomic responses and adaptive behaviour, and that it makes a unique contribution to the development and persistence of psychiatric disorders.