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首页> 外文期刊>Nucleic Acids Research >Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells
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Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells

机译：沉默的人类CDH1基因CpG岛的CpG岛的染色质成分的修饰和参与的异质性

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The structural alteration of chromatin has a key role in regulating gene expression. The alteration of chromatin is mediated by modification of its components. Detailed understanding of the relationship between these modifications, notably, methylation of the full-length CpG island, the association of methyl-CpG binding proteins (MBPs), and the acetylation and methylation of histones in gene silencing is vitally important. Currently, however, the manner in which chromatin components, associated with a specific gene, are modified is poorly understood. Here we provide in vivo evidence in cancer cells of the differential association between CpG methylation, MBPs, and histone modification in the entire CpG island of the human E-cadherin (CDH1) gene. Of the cell lines with CDH1 transcriptional repression, the distribution of methyl-CpGs in the CpG island differed markedly. In a cell line with gene silencing, the promoter region was almost methylation-free. Chromatin immunoprecipitation analysis revealed that the acetylation status of histone H4 differed between cell lines. However, deacetylated histone H3 was associated with the CpG island in all silenced cell lines. Binding of MeCP2 was also detected in all silenced cell lines. Additional binding of MBD1 protein was detected in a cell line in which the promoter region was poorly methylated and only histone H3 was deacetylated. Binding of MBD2 protein was detected in all other silenced cell lines. Histone H3 lysine 9 was methylated in all silenced cells, while histone H3 lysine 4 was methylated in some silenced cell lines. These results demonstrate that chromatin components associated with inactive CDH1 chromatin is heterogeneously modified and suggests the presence of multiple pathways for the formation of inactive chromatin.
机译：染色质的结构改变在调节基因表达中起关键作用。染色质的改变是由其成分的修饰介导的。详细了解这些修饰之间的关系，特别是全长CpG岛的甲基化，甲基CpG结合蛋白（MBP）的关联以及基因沉默中组蛋白的乙酰化和甲基化至关重要。然而，目前，人们对与特定基因相关的染色质组分修饰的方式了解甚少。在这里，我们提供了体内癌细胞中人E-钙粘蛋白（CDH1）基因整个CpG岛中CpG甲基化，MBP和组蛋白修饰之间差异关联的体内证据。在具有CDH1转录抑制作用的细胞系中，甲基CpGs在CpG岛中的分布明显不同。在具有基因沉默的细胞系中，启动子区域几乎没有甲基化。染色质免疫沉淀分析表明，组蛋白H4的乙酰化状态在细胞系之间有所不同。然而，在所有沉默细胞系中，去乙酰化的组蛋白H3与CpG岛有关。在所有沉默的细胞系中也检测到MeCP2的结合。在启动子区域甲基化较弱且仅组蛋白H3脱乙酰化的细胞系中检测到MBD1蛋白的其他结合。在所有其他沉默的细胞系中检测到MBD2蛋白的结合。组蛋白H3赖氨酸9在所有沉默细胞中均被甲基化，而组蛋白H3赖氨酸4在某些沉默细胞系中被甲基化。这些结果表明，与非活性CDH1染色质相关的染色质组分被异质修饰，并表明存在多种形成非活性染色质的途径。

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