Abstract: International audience ; Epigenetic marks are established according to the environment and individual experiences. During brain development, they participate to the activity of neural circuits and contribute to the establishment and maintenance of several behaviours. Among them, cytosine methylation (5mC), one of the most studied modifications in the brain, is particularly sensitive to adverse environments. Recently, cytosine hydroxymethylation (5hmC), an abundant and stable mark derived from 5mC found in synaptic genes and enriched in fetal brain, has emerged as another major contributor to behavioral disturbances. , but is still a bottleneck. We successfully developed a method to quantify the respective contributions of 5mC and 5hmC in the modulation of cognitive functions related to olfaction observed in mice male offspring born to control dams or dams that have been fed a high-fat diet before a preconception weight loss (WL) (Panchenko et al., 2019; Safi-Stibler et al., 2020). Our findings reveal an average level of 20.2% or of 5.5% for 5mC and 5hmC in the olfactory bulb, respectively. One-third of genes are co-regulated by both DNA modifications and differentially methylated and hydroxymethylated cytosines address different functions. These results underscore the need to distinguish the roles of 5mC and 5hmC to fully understand the influence of maternal environment on brain development.
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