<p>Posttranslational modifications of histones, in particular histone H3, play a key role in the regulation of transcription, which directly affects learning and memory processes. Among the most studied modifications of histone H3 is lysine methylation in the 4th position (H3K4me3), the level of which significantly increases with the formation of the conditioned reflex fear. At the same time, glutamine in the 5th position (Q5) of histone H3 undergoes another epigenetic modification – serotonylation. Despite the fact that histone H3 serotonylation at the Q5 position represents an important family of epigenetic markers in the brain that play a critical role in permissive gene expression, the functional significance of the joint H3 modification H3K4me3Q5ser remains almost unexplored. In this paper, we analyzed the dynamics of modification of the H3K4me3Q5ser in the rat brain during the fear conditioning paradigm using combined behavioral and molecular approaches. We showed that in the CA1 hippocampal area there is a significant decrease in the H3K4me3Q5ser levels in response to the presentation of a new context (novelty). Fear conditioning also led to a significant decrease in serotonylation levels compared to the basal levels in the naïve control group. Thus, the data obtained indicate that novelty and fear conditioning significantly change the basal patterns of posttranslational histone modifications and are associated with a decrease in histone H3 serotonylation in the hippocampus.</p>