Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice
Abstract Background Maternal 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...
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BMC
2018-02-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-018-4479-2 |
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| author | Nikita I. Ershov Natalya P. Bondar Arina A. Lepeshko Vasiliy V. Reshetnikov Julia A. Ryabushkina Tatiana I. Merkulova |
| author_facet | Nikita I. Ershov Natalya P. Bondar Arina A. Lepeshko Vasiliy V. Reshetnikov Julia A. Ryabushkina Tatiana I. Merkulova |
| author_sort | Nikita I. Ershov |
| collection | DOAJ |
| description | Abstract Background Maternal 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. Results In 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. Conclusion The 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. |
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| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-17T07:25:15Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-04f6841db340467db6fa999bdd4a3cd02022-12-21T21:58:39ZengBMCBMC Genomics1471-21642018-02-0119S3394910.1186/s12864-018-4479-2Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult miceNikita I. Ershov0Natalya P. Bondar1Arina A. Lepeshko2Vasiliy V. Reshetnikov3Julia A. Ryabushkina4Tatiana I. Merkulova5Laboratory of Gene Expression Regulation, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesLaboratory of Gene Expression Regulation, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesLaboratory of Gene Expression Regulation, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesLaboratory of Gene Expression Regulation, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesNovosibirsk National Research State UniversityLaboratory of Gene Expression Regulation, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesAbstract Background Maternal 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. Results In 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. Conclusion The 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.http://link.springer.com/article/10.1186/s12864-018-4479-2ChIP-seqEarly life stressMaternal separationHandlingH3K4me3Prefrontal cortex |
| spellingShingle | Nikita I. Ershov Natalya P. Bondar Arina A. Lepeshko Vasiliy V. Reshetnikov Julia A. Ryabushkina Tatiana I. Merkulova Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice BMC Genomics ChIP-seq Early life stress Maternal separation Handling H3K4me3 Prefrontal cortex |
| title | Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice |
| title_full | Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice |
| title_fullStr | Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice |
| title_full_unstemmed | Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice |
| title_short | Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice |
| title_sort | consequences of early life stress on genomic landscape of h3k4me3 in prefrontal cortex of adult mice |
| topic | ChIP-seq Early life stress Maternal separation Handling H3K4me3 Prefrontal cortex |
| url | http://link.springer.com/article/10.1186/s12864-018-4479-2 |
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