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首页> 外文期刊>Epigenetics & Chromatin >A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci
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A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

机译：人类胚胎干细胞的全基因组筛选揭示了与已知疾病位点相关的等位基因特异性组蛋白修饰的新位点

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Background Chromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs). Results Using a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders. Conclusion These results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.
机译：背景在给定位置的染色质结构在细胞中的染色体拷贝之间可能会有所不同，并且染色质结构的这种不平衡已被证明对理解控制几个疾病位点的分子机制很重要。人类遗传变异，DNA甲基化和疾病已被深入研究，发现了等位基因特异性DNA甲基化（ASM）的许多位点。但是，关于等位基因特异性组蛋白修饰（ASHM）的位点在全基因组范围内的发生及其与人类疾病的关系知之甚少。这项研究的目的是调查人类胚胎干细胞（hESCs）中ASHM位点的范围和特征。结果我们使用统计严格的协议，研究了hESCs中ASHM的基因组分布，以及它们与等位基因特异性表达（ASE）和DNA甲基化位点的关系。我们发现，尽管它们很少见，但在显示ASE的基因座上ASHM的位点却大量富集。在已知的印迹区域也发现了许多，因此ASHM的位点比ASM的位置更可能是印迹区域的标记。我们还发现hESCs中ASHM和ASE的位点共同定位于由缺失介导的发育综合征的危险基因座，从而为这些疾病的病因学提供了见识。结论这些结果证明了ASHM模式在解释疾病位点方面的潜在重要性，并且所描述的方案为在其他细胞类型中进行ASHM的类似研究提供了基础，以进一步了解人类疾病的易感性。

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