Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice

Abstract

BackgroundMaternal separation models in rodents are widely used to establish molecular mechanisms underlying prolonged effects of early life adversity on neurobiological and behavioral outcomes in adulthood. However, global epigenetic signatures following early life stress in these models remain unclear.ResultsIn this study, we carried out a ChIP-seq analysis of H3K4 trimethylation profile in the prefrontal cortex of adult male mice with a history of early life stress. Two types of stress were used: prolonged separation of pups from their mothers (for 3 h once a day, maternal separation, MS) and brief separation (for 15 min once a day, handling, HD). Adult offspring in the MS group demonstrated reduced locomotor activity in the open field test accompanied by reduced exploratory activity, while the HD group showed decreased anxiety-like behavior only. In a group of maternal separation, we have found a small number (45) of slightly up-regulated peaks, corresponding to promoters of 70 genes, while no changes were observed in a group of handling. Among the genes whose promoters have differential enrichment of H3K4me3, the most relevant ones participate in gene expression regulation, modulation of chromatin structure and mRNA processing. For two genes, Ddias and Pip4k2a, increased H3K4me3 levels were associated with the increased mRNA expression in MS group.ConclusionThe distribution of H3K4me3 in prefrontal cortex showed relatively low variability across all individuals, and only some subtle changes were revealed in mice with a history of early life stress. It is possible that the observed long-lasting behavioral alterations induced by maternal separation are mediated by other epigenetic mechanisms, or other brain structures are responsible for these effects.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4479-2) contains supplementary material, which is available to authorized users.

Circadian clock mechanism driving mammalian photoperiodism

“…To determine if epigenetic changes in H3K4me3 marks were associated with transcriptional activation we first improved the sheep genome annotation of transcripts and transcription start sites (TSSs) with PT RNA and a combination of Cap Analysis of Gene Expression (CAGE-seq, Supplementary Data 4) 32 and ISOSEQ long-read RNA-seq (SRA: PRJNA391103, see methods for details). Using this improved annotation we identified H3K4me3 peaks and found the distribution on genomic features to be similar to previous studies [33][34][35] , validating our approach (see methods section).…”

Circadian clock mechanism driving mammalian photoperiodism

“…To determine if epigenetic changes in H3K4me3 marks were associated with transcriptional activation we first improved the sheep genome annotation of transcripts and transcription start sites (TSS) with PT RNA and a combination of Cap Analysis of Gene Expression (CAGE-seq, Supplementary Data 4) 32 and ISOSEQ long-read RNA-seq (SRA: PRJNA391103, see methods for details). Using this improved annotation we identified H3K4me3 peaks and found the distribution on genomic features to be similar to previous studies [33][34][35] , validating our approach (see methods section). Next we identified seasonally expressed genes, as defined by RNA-seq analysis of differentially regulated genes (DEGs) in the SP to LP and LP to SP transfers (Supplementary Data 3), and observed a strong correlation between seasonal gene expression and H3K4me3 peaks around the transcription start sites (TSS's)( Fig.…”

“…We clustered SP and LP time-series profiles using Partitioning Around Medoids (PAM) ( Fig. 4g) peaks were closely resembling to the previous reports 33,34 ( Supplementary Fig. 6a).…”

Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

“…DNA methylation in the NR1D1 promoter is greater in humans with a history of child abuse [55]. In our study of delayed effects of early-life stress on the genomic landscape of H3K4me3 in adult male mice [56], there was a significant increase in the amount of active-chromatin modification H3K4me3 in the promoter region of Nr1d1. These data are suggestive of a more active promoter of this gene in the animals with a history of MS.…”