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Proteomic Characterisation of Posttranslational Modifications of Histone Proteins in the Prenatally Stressed Mouse Brain

机译:产前应激小鼠脑中组蛋白蛋白质翻译后修饰的蛋白质组学表征。

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摘要

Genetic factors have been widely implicated in the study of schizophrenia. Twin and adoption studies estimate the heritability at approximately 80%. The rate of discordance between monozygotic twins is estimated at 65%, indicating that other factors influence the risk of developing schizophrenia. Many environmental factors have been identified that affect oneu27s likelihood of developing this disorder. Examples of these factors include exposure to drugs, psychological stress and nutritional deficiencies, especially during critical time periods, such as prenatal and adolescence periods [1, 2].This implies that the interplay between genetic and environmental factors is important in the development of schizophrenia but the mechanism by which external influences affect oneu27s gene expression is poorly understood. Epigenetics provides one mechanism by which these factors may interact to contribute to disease. Epigenetic information is inherited via alterations to DNA methylation patterns, histone posttranslational modifications (hPTMs) and microRNA expression aberration [1-3]. These are thought to modify gene and subsequent protein expression and contribute to disease risk. Critically, these alterations can occur without a change in the underlying genetic code and are thus termed u27epigeneticu27. Epigenetic modifications can be induced by environmental factors [1-3].The aim of this project was to optimise a technique to identify hPTMs in brain regions implicated in schizophrenia using mass spectrometry. As part of this project, the technique was applied to the hippocampus of a prenatal stress mouse model that been shown to mimic certain features of schizophrenia. The intention of the technique is to assess the influence of environment on gene expression levels via hPTMs in this mouse model.Overall, twenty-six hPTMs were observed in prenatally stressed and control groups. The hPTMs were searched against relevant databases to evaluate previously associated gene expression states and diseases. Future studies will attempt to quantify hPTM expression intensities to compare differential expression levels between model and control samples. Through the identification of new and differentially expressed hPTMs in prenatally stressed and control samples, this technique has the potential to provide important insights into the epigenetic mechanism of schizophrenia.
机译:遗传因素已广泛涉及精神分裂症的研究。双胞胎和收养研究估计遗传力约为80%。单卵双胞胎之间的不一致率估计为65%,这表明其他因素会影响患精神分裂症的风险。已经发现许多环境因素会影响人们患上这种疾病的可能性。这些因素的例子包括接触药物,心理压力和营养缺乏,尤其是在关键时期,例如产前和青春期[1,2]。这表明遗传因素和环境因素之间的相互作用在精神分裂症的发展中很重要。但外界影响其基因表达的机制了解甚少。表观遗传学提供了一种机制,通过这些机制,这些因素可能相互作用以促成疾病。表观遗传信息是通过改变DNA甲基化模式,组蛋白翻译后修饰(hPTM)和microRNA表达异常来继承的[1-3]。这些被认为会修饰基因和随后的蛋白质表达,并增加疾病风险。至关重要的是,这些改变可以在不改变基础遗传密码的情况下发生,因此被称为表观遗传的。表观遗传修饰可以由环境因素诱导[1-3]。该项目的目的是优化一种利用质谱法鉴定与精神分裂症有关的大脑区域中hPTM的技术。作为该项目的一部分,该技术被应用于产前应激小鼠模型的海马,该小鼠模型被证明可以模仿精神分裂症的某些特征。该技术的目的是通过此小鼠模型中的hPTM评估环境对基因表达水平的影响。总体上,在产前应激和对照组中观察到26种hPTM。在相关数据库中搜索了hPTM,以评估先前相关的基因表达状态和疾病。未来的研究将试图量化hPTM表达强度,以比较模型和对照样品之间的差异表达水平。通过鉴定产前应激和对照样品中新的和差异表达的hPTM,该技术有可能为精神分裂症的表观遗传机制提供重要见解。

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    Brindley Elizabeth;

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