Figure 6.

Low-novelty-seeking animals (LRs) exhibit a coordinated epigenetic regulation of the bdnf promoter 6 following social defeat, coherent with a transcriptional activation, whereas high-novelty-seeking animals (HRs) do not. The hippocampal bdnf promoter 6 is represented, associated with its regulation of histone modifications and corresponding epigenetic factors at baseline (top) and following acute (middle) or repeated defeat (bottom) in LR (left) and HR (right) animals. Following the first defeat session, LR animals display an upregulation of the K-acetyltransferases CBP and H3K4-specific methyltransferase Mll1, resulting in higher H3 acetylation and H3K4me² (middle, left). Interestingly, an increase of the H3K9-specific demethylase is also observed, leading to the removal of the repressive H3K9me², which, unlike Kdm3a, is maintained following repeated exposure to the defeat (bottom, left). Similar to H3K9me², the increases of H3K4me², AcK9K14H3, Mll1, and CBP are also maintained after repeated defeat, promoting transcriptional activation of BDNF exon VI and resilience to social defeat. Compared with LR animals, HR animals exhibit at baseline (top, right) higher H3K4me², CBP, and Mll1 levels, which, associated with lower H3K9me², result in higher BDNF exon VI mRNA levels. Following repeated social defeat, however, only a slight increase in Kdm3a is observed but does not induce any further transcriptional activation, therefore leaving HR animals vulnerable to the social defeat. Arrows indicate increases in mRNA levels proportional to their width, compared with nondefeated animals (baseline) of the same phenotype.