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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Active cytosine dernethylation triggered by a nuclear receptor involves DNA strand breaks
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Active cytosine dernethylation triggered by a nuclear receptor involves DNA strand breaks

机译:核受体触发的主动胞嘧啶脱甲基化涉及DNA链断裂

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Cytosine methylation at CpG dinucleotides contributes to the epigenetic maintenance of gene silencing. Dynamic reprogramming of DNA methylation patterns is believed to play a key role during development and differentiation in vertebrates. The mechanisms of DNA demethylation remain unclear and controversial. Here, we present a detailed characterization of the demethylation of an endogenous gene in cultured cells. This demethylation is triggered in a regulatory region by a transcriptional activator, the glucocorticoid receptor. We show that DNA demethylation is an active process, occurring independently of DNA replication, and in a distributive manner without concerted demethylation of cytosines on both strands. We demonstrate that the DNA backbone is cleaved 3' to the methyl cytidine during demethylation, and we suggest that a DNA repair pathway may therefore be involved in this demethylation.
机译:CpG二核苷酸处的胞嘧啶甲基化有助于基因沉默的表观遗传维持。 DNA甲基化模式的动态重编程被认为在脊椎动物的发育和分化过程中起着关键作用。 DNA脱甲基化的机制仍不清楚和有争议。在这里,我们提出了培养细胞中内源基因的去甲基化的详细表征。该脱甲基化在转录调控因子糖皮质激素受体的调节区域内触发。我们表明,DNA去甲基化是一个活跃的过程,独立于DNA复制而发生,并且以分布式方式在两条链上都没有胞嘧啶的一致去甲基化。我们证明DNA骨架在去甲基化过程中被3'裂解为甲基胞嘧啶,并且我们建议DNA修复途径可能因此参与该去甲基化。

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