Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches
| Autor: | Theresa S. Totah, Keith W. Dunaway, Annie Vogel Ciernia, Rochelle L. Coulson, Akanksha Singh-Taylor, Janine M. LaSalle, Benjamin I. Laufer, Danielle S. Stolzenberg, Dag H. Yasui, Tallie Z. Baram, Charles E. Mordaunt, Jaime C. Frahm |
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| Rok vydání: | 2017 |
| Předmět: |
Epigenomics
Male 0301 basic medicine Cancer Research Bisulfite sequencing Hypothalamus Embryonic Development Genomics Computational biology Biology Bioinformatics 03 medical and health sciences 0302 clinical medicine Gene expression Neuroplasticity microRNA Animals Humans Molecular Biology Gene Research Articles 030304 developmental biology 0303 health sciences Neuronal Plasticity Whole Genome Sequencing Sequence Analysis RNA Gene Expression Profiling Gene Expression Regulation Developmental Sequence Analysis DNA DNA Methylation Phenotype Mother-Child Relations Rats MicroRNAs 030104 developmental biology Differentially methylated regions DNA methylation CpG Islands Female Neuroscience Stress Psychological 030217 neurology & neurosurgery |
| Popis: | BackgroundMaternal care during early-life plays a crucial role in the sculpting of the mammalian brain. Augmented maternal care during the first postnatal week promotes life-long stress resilience and improved memory compared with the outcome of routine rearing conditions. Recent evidence suggests that this potent phenotypic change commences with altered synaptic connectivity of stress sensitive hypothalamic neurons. However, the epigenomic basis of the long-lived consequences is not well understood.MethodsHere, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to examine the effects of augmented maternal care on DNA cytosine methylation, gene expression, and miRNA expression.ResultsA significant decrease in global DNA methylation was observed in offspring hypothalamus following a week of augmented maternal care, corresponding to differential methylation and expression of thousands of genes. Differentially methylated and expressed genes were enriched for functions in neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation, as well as known stress response genes. Twenty prioritized genes with three lines of evidence (methylation, expression, and altered miRNA target) were identified as highly relevant to the stress resiliency phenotype.ConclusionsThis combined unbiased approach enabled the discovery of novel genes and gene pathways that advance our understanding of the central epigenomic mechanisms underlying the profound effects of maternal care on the developing brain. |
| Databáze: | OpenAIRE |
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