Early life stress increases chromatin accessibility in the adult Nucleus Accumbens, Mayowa Oke, UG '22 (3964408)
Early life stress (ELS) is a term which describes a variety of forms of childhood adversity. Research involving both human and rodent subjects has shown that individuals who experience ELS are at higher risk of developing psychiatric disorders following a second experience (or, “hit”) of stress in adulthood. Studies with rodent models have allowed for the discovery that this sensitization to stress is accompanied by unique transcriptional patterns in key reward regions such as the nucleus accumbens (NAc). These behavioural and transcriptional results together suggest that epigenetic mechanisms may play a role in the sensitization of stress following ELS. We hypothesized that epigenetic mechanisms may prime chromatin to adopt an open but not active state after an experience of early life stress, and that these regions of chromatin may become active following additional future stress. To investigate this question, we used ATAC-seq to analyze chromatin accessibility in the NAc of adult mice that had experienced ELS. We also compared the chromatin accessibility data from this experiment with earlier discoveries in NAc cells from juvenile mice that underwent ELS. My analysis found that ELS induces chromatin to adopt a more accessible conformation into adulthood, primarily at intergenic regions. This suggests that an enhancer priming mechanism may underlie the unique transcriptional patterns observed following two-hits of stress. Moreover, further analysis reveals that most of our changes to chromatin accessibility occur in or around genes relevant for psychiatric development, further suggesting that chromatin regulation following ELS may underlie increased susceptibility to psychiatric illnesses.