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Distinguishing epigenetic marks of developmental and imprinting regulation

机译:区分发育和印迹调控的表观遗传标记

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Background The field of epigenetics is developing rapidly, however we are only beginning to comprehend the complexity of its influence on gene regulation. Using genomic imprinting as a model we examine epigenetic profiles associated with different forms of gene regulation. Imprinting refers to the expression of a gene from only one of the chromosome homologues in a parental-origin-specific manner. This is dependent on heritable germline epigenetic control at a cis-acting imprinting control region that influences local epigenetic states. Epigenetic modifications associated with imprinting regulation can be compared to those associated with the more canonical developmental regulation, important for processes such as differentiation and tissue specificity. Here we test the hypothesis that these two mechanisms are associated with different histone modification enrichment patterns. Results Using high-throughput data extraction with subsequent analysis, we have found that particular histone modifications are more likely to be associated with either imprinting repression or developmental repression of imprinted genes. H3K9me3 and H4K20me3 are together enriched at imprinted genes with differentially methylated promoters and do not show a correlation with developmental regulation. H3K27me3 and H3K4me3, however, are more often associated with developmental regulation. We find that imprinted genes are subject to developmental regulation through bivalency with H3K4me3 and H3K27me3 enrichment on the same allele. Furthermore, a specific tri-mark signature comprising H3K4me3, H3K9me3 and H4K20me3 has been identified at all imprinting control regions. Conclusion A large amount of data is produced from whole-genome expression and epigenetic profiling studies of cellular material. We have shown that such publicly available data can be mined and analysed in order to generate novel findings for categories of genes or regulatory elements. Comparing two types of gene regulation, imprinting and developmental, our results suggest that different histone modifications associate with these distinct processes. This form of analysis is therefore a useful tool to elucidate the complex epigenetic code associated with genome function and to determine the underlying features conferring epigenetic states.
机译:背景技术表观遗传学的领域正在迅速发展,但是我们才刚刚开始理解其对基因调控的影响的复杂性。使用基因组印迹作为模型,我们检查了与不同形式的基因调控相关的表观遗传概况。印记是指以亲本来源特异性的方式仅从一个染色体同源物中表达基因。这取决于在影响局部表观遗传状态的顺式作用印迹控制区域的可遗传种系表观遗传控制。可以将与印迹调控相关的表观遗传修饰与与更规范的发育调控相关的修饰相比较,这对于诸如分化和组织特异性的过程很重要。在这里,我们测试了这两种机制与不同的组蛋白修饰富集模式相关的假设。结果使用高通量数据提取和后续分析,我们发现特定的组蛋白修饰更可能与印迹基因的印迹抑制或发育抑制相关。 H3K9me3和H4K20me3在一起富含差异甲基化启动子的印迹基因上均富集,并且与发育调控没有相关性。但是,H3K27me3和H3K4me3更经常与发育调控相关。我们发现印迹的基因受同等位基因上H3K4me3和H3K27me3富集的双价性的发育调控。此外,已经在所有压印控制区域识别出包括H3K4me3,H3K9me3和H4K20me3的特定三标记签名。结论从细胞材料的全基因组表达和表观遗传学分析中获得了大量数据。我们已经表明,可以挖掘和分析这样的公共可用数据,以便针对基因或调控元件的类别产生新颖的发现。比较两种类型的基因调节,印迹和发育,我们的结果表明,不同的组蛋白修饰与这些不同的过程相关。因此,这种形式的分析是阐明与基因组功能相关的复杂表观遗传密码并确定赋予表观遗传状态的潜在特征的有用工具。

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