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首页> 外文期刊>Molecular and Cellular Biology >Acetylation-Induced Transcription Is Required for Active DNA Demethylation in Methylation-Silenced Genes
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Acetylation-Induced Transcription Is Required for Active DNA Demethylation in Methylation-Silenced Genes

机译：乙酰化诱导的基因的甲基化沉默基因中的活性DNA去甲基化需要转录。

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A hallmark of vertebrate genes is that actively transcribed genes are hypomethylated in critical regulatory sequences. However, the mechanisms that link gene transcription and DNA hypomethylation are unclear. Using a trichostatin A (TSA)-induced replication-independent demethylation assay with HEK 293 cells, we show that RNA transcription is required for DNA demethylation. Histone acetylation precedes but is not sufficient to trigger DNA demethylation. Following histone acetylation, RNA polymerase II (RNAP II) interacts with the methylated promoter. Inhibition of RNAP II transcription with actinomycin D, α-amanitin, or CDK7-specific small interfering RNA inhibits DNA demethylation. H3 trimethyl lysine 4 methylation, a marker of actively transcribed genes, was associated with the cytomegalovirus promoter only after demethylation. TSA-induced demethylation of the endogenous cancer testis gene GAGE follows a similar sequence of events and is dependent on RNA transcription as well. These data suggest that DNA demethylation follows rather than precedes early transcription and point towards a novel function for DNA demethylation as a memory of actively transcribed genes.
机译：脊椎动物基因的标志是，主动转录的基因在关键的调控序列中被甲基化。但是，连接基因转录和DNA低甲基化的机制尚不清楚。使用曲古抑菌素A（TSA）诱导的HEK 293细胞的复制独立的脱甲基化分析，我们显示RNA转录是DNA脱甲基所必需的。组蛋白乙酰化先于但不足以触发DNA脱甲基。组蛋白乙酰化后，RNA聚合酶II（RNAP II）与甲基化的启动子相互作用。用放线菌素D，α-amanitin或CDK7特异性小干扰RNA抑制RNAP II转录可抑制DNA脱甲基。 H3三甲基赖氨酸4甲基化，一个活跃转录的基因的标记，只有在脱甲基后才与巨细胞病毒启动子相关。 TSA诱导的内源性睾丸基因 GAGE 的去甲基化遵循相似的事件序列，并且也依赖于RNA转录。这些数据表明DNA去甲基化是在早期转录之后而不是在其之前，并且指出了DNA去甲基化作为一种​​活性转录基因的记忆的新功能。

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