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DNA Methylation Dictates Histone H3K4 Methylation

机译：DNA甲基化听写组蛋白H3K4甲基化

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Histone lysine methylation and DNA methylation contribute to transcriptional regulation. We have previously shown that acetylated histones are associated with unmethylated DNA and are nearly absent from the methylated DNA regions by using patch-methylated stable episomes in human cells. The present study further demonstrates that DNA methylation immediately downstream from the transcription start site has a dramatic impact on transcription and that DNA methylation has a larger effect on transcription elongation than on initiation. We also show that dimethylated histone H3 at lysine 4 (H3K4me2) is depleted from regions with DNA methylation and that this effect is not linked to the transcriptional activity in the region. This effect is a local one and does not extend even 200 bp from the methylated DNA regions. Although depleted primarily from the methylated DNA regions, the presence of trimethylated histone H3 at lysine 4 (H3K4me3) may be affected by transcriptional activity as well. The data here suggest that DNA methylation at the junction of transcription initiation and elongation is most critical in transcription suppression and that this effect is mechanistically mediated through chromatin structure. The data also strongly support the model in which DNA methylation and not transcriptional activity dictates a closed chromatin structure, which excludes H3K4me2 and H3K4me3 in the region, as one of the pathways that safeguards the silent state of genes.
机译：组蛋白赖氨酸甲基化和DNA甲基化有助于转录调控。先前我们已经证明，乙酰化组蛋白与未甲基化的DNA相关联，并且通过在人细胞中使用贴片甲基化的稳定附加体，甲基化DNA区域几乎不存在。本研究进一步证明，紧邻转录起始位点下游的DNA甲基化对转录具有显着影响，并且DNA甲基化对转录延伸的影响大于对起始的影响。我们还显示，赖氨酸4（H3K4me2）处的二甲基化组蛋白H3从具有DNA甲基化的区域消耗掉，并且这种作用与该区域的转录活性无关。这种作用是局部的，甚至不从甲基化的DNA区域延伸200bp。尽管主要从甲基化的DNA区域中耗尽，但是赖氨酸4（H3K4me3）上三甲基化的组蛋白H3的存在也可能受到转录活性的影响。此处的数据表明，在转录抑制和启动过程中，转录起始和延伸连接处的DNA甲基化是最关键的，这种作用是通过染色质结构以机械方式介导的。数据也有力地支持了该模型，在该模型中，DNA甲基化而不是转录活性决定了封闭的染色质结构，该结构不包括该区域中的H3K4me2和H3K4me3，是保护基因沉默状态的途径之一。

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