DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism.
DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism.
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DOI：
10.1038/srep33222
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发表时间：
2016-09-15
影响因子：
4.6
通讯作者：
Avvedimento EV
中科院分区：
文献类型：
--
作者：
Russo G;Landi R;Pezone A;Morano A;Zuchegna C;Romano A;Muller MT;Gottesman ME;Porcellini A;Avvedimento EV
我们的特点在染色质结构，DNA甲基化和转录过程中和同源DNA修复（HR）后的变化。我们发现HR修饰了修复片段的DNA甲基化模式。HR还通过诱导连接修复基因5′和3′端的DNA染色质环来改变局部组蛋白H3甲基化以及染色质结构。在修复后的两周内，由碱基切除修复酶促进的转录相关的去甲基化进一步修饰修复的DNA的甲基化。随后，修复的基因显示稳定但多样的甲基化谱。这些谱控制每个克隆中的表达水平。我们的数据表明，HR诱导的DNA甲基化和染色质重塑可能是体细胞基因表达永久性变异的来源。
We characterize the changes in chromatin structure, DNA methylation and transcription during and after homologous DNA repair (HR). We find that HR modifies the DNA methylation pattern of the repaired segment. HR also alters local histone H3 methylation as well chromatin structure by inducing DNA-chromatin loops connecting the 5′ and 3′ ends of the repaired gene. During a two-week period after repair, transcription-associated demethylation promoted by Base Excision Repair enzymes further modifies methylation of the repaired DNA. Subsequently, the repaired genes display stable but diverse methylation profiles. These profiles govern the levels of expression in each clone. Our data argue that DNA methylation and chromatin remodelling induced by HR may be a source of permanent variation of gene expression in somatic cells.
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