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Großgerät: Messplatz für epigenetische Untersuchungen
Epigenetics is most commonly defined as the ensemble of alterations in gene functions that are heritable through both mitosis and meiosis, but that cannot be explained by changes in the DNA sequence itself. At the molecular level, epigenetic mechanisms are biochemical modifications of the DNA and histone proteins, the major constituents of chromatin. From the biochemical point of view epigenetic mechanisms include direct modifications of the DNA at specific sites, i.e. through DNA-methylation and very specific modifications of histone proteins. These posttranslational modifications of the histone proteins are regulated for example through acetylation, methylation, phosphorylation and ubiquitination. While acetylation and phosphorylation of histones in principle lead to enhanced gene expression, methylation (mono-, di- or trimehylation) can result in both actively transcribed and silenced genes. Histone modifications are regulated by the specific interaction of enzymes such as DNA methyltransferases, histone acetyltransferases, histone deacetylases and histone methyltransferases. Epigenetic mechanisms are involved in brain development and there is increasing evidence that epigenetic events also mediate synaptic plasticity induced by environmental stimuli, including learning and emotional experience. The overarching aim of our ongoing projects is to analyze epigenetic modifications in response to pre-reproductive and prenatal stress, neonatal trauma and neglect, and to test the hypothesis that epigenetic changes are involved in dendritic and synaptic reorganization, which occurs in respone to prenatal and neonatal stress exposure . Since many of the mental disorders associated with perinatal stress exhibit a sex bias, the epigenetic analysis of how sex-specific vulnerability and resilience arises will improve our mechanistic insight, leading to the identification of novel targets for protective and therapeutic development. Thus, we aim to identify sex-specific differences in DNA methylation and chromatin remodeling in response to perinatal and pre-reproductive stress, childhood maltreatment and neglect.
DNA Methylierung, Gehirnentwicklng, Histonmodifikation, Psychische Störungen
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