Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice
Autor: | Julia A. Ryabushkina, Arina A. Lepeshko, Vasiliy V. Reshetnikov, Tatiana I. Merkulova, Natalya P. Bondar, Nikita I. Ershov |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty lcsh:QH426-470 lcsh:Biotechnology Emotions Biology Methylation Prefrontal cortex Open field Histones 03 medical and health sciences Mice 0302 clinical medicine Internal medicine lcsh:TP248.13-248.65 Adaptation Psychological Genetics medicine Animals Epigenetics Maternal separation Gene Regulation of gene expression Behavior Animal Research Lysine Maternal Deprivation Handling Promoter Genomics Early life stress H3K4me3 Chromatin Mice Inbred C57BL ChIP-seq lcsh:Genetics 030104 developmental biology Endocrinology Female 030217 neurology & neurosurgery Stress Psychological Biotechnology |
Zdroj: | BMC Genomics, Vol 19, Iss S3, Pp 39-49 (2018) BMC Genomics |
ISSN: | 1471-2164 |
DOI: | 10.1186/s12864-018-4479-2 |
Popis: | 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. Electronic supplementary material The online version of this article (10.1186/s12864-018-4479-2) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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