Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: An impact of early-life stress.

Chronic stress is the leading risk factor of a broad range of severe psychopathologies. Nonetheless, the molecular mechanisms triggering these pathological processes are not well understood. In our study, we investigated the effects of 15-day social defeat stress (SDS) on the genome-wide landscape of trimethylation at the 4th lysine residue of histone H3 (H3K4me3) and on the transcriptome in the prefrontal cortex of mice that were reared normally (group SDS) or subjected to maternal separation early in life (group MS+SDS). The mice with the history of stress early in life showed increased susceptibility to SDS in adulthood and demonstrated long-lasting genome-wide alterations in gene expression and splicing as well as in the H3K4me3 epigenetic landscape in the prefrontal cortex. Thus, the high-throughput techniques applied here allowed us to simultaneously detect, for the first time, genome-wide epigenetic and transcriptional changes in the murine prefrontal cortex that are associated with both chronic SDS and increased susceptibility to this stressor.

Data of correlation analysis between the density of H3K4me3 in promoters of genes and gene expression: Data from RNA-seq and ChIP-seq analyses of the murine prefrontal cortex.

H3K4me3 is typically found in the promoter region of genes and is a mark associated with an open chromatin state and active gene transcription. Nonetheless, the role of H3K4me3 in the regulation of transcription is still debated. To improve the understanding of the connection between H3K4me3 density in promoters and gene expression, we assessed the correlation between these two parameters. We utilized genome-wide high-throughput RNA sequencing (RNA-seq) data and H3K4me3-based chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq), carried out on the same samples of the prefrontal cortex from 10 male C57Bl6 mice with different stress experience [Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: an impact of early-life stress, 1]. In addition, we assessed the correlation between H3K4me3 density and gene expression in datasets of cell-specific genes. Altogether, the results are useful for the elucidation of H3K4me3 involvement in the regulation of transcription in the murine prefrontal cortex.