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Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks

机译:组蛋白H2A.Z和DNA甲基化是相互拮抗的染色质标记

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Eukaryotic chromatin is separated into functional domains differentiated by post-translational histone modifications, histone variants and DNA methylation. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are crucial for eukaryotic development, and aberrant methylation-induced silencing of tumour suppressor genes is a common feature of human cancer. In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swrl ATPase complex near 5' ends of genes where it promotes transcriptional competence. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation, engenders opposite changes (gains and losses) in H2A.Z deposition, whereas mutation of the PIE1 subunit of the Swrl complex that deposits H2A.Z leads to genome-wide hyper-methylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation.
机译:真核染色质被分为功能区,通过翻译后组蛋白修饰,组蛋白变体和DNA甲基化来区分。甲基化与植物和动物中转录起始的抑制有关,并且经常在转座因子中发现。正确的甲基化模式对于真核生物发育至关重要,而异常甲基化诱导的肿瘤抑制基因沉默是人类癌症的共同特征。与甲基化相反,组蛋白变体H2A.Z优先通过Swrl ATPase复合物沉积在基因的5'端附近,从而促进转录能力。 DNA甲基化和H2A.Z如何影响转录仍然是未知的。在这里,我们显示出在植物拟南芥中,DNA甲基化区域在H2A.Z中数量不足。在活跃转录的基因体内和甲基化的转座子中,在DNA甲基化位点可以看到H2A.Z的排除。 MET1 DNA甲基转移酶的突变既造成DNA甲基化的损失,又导致DNA甲基化的增加,在H2A.Z沉积物中产生相反的变化(增益和损失),而沉积H2A.Z的Swrl复合体的PIE1亚基的突变导致基因组-广泛的超甲基化。我们的发现表明,DNA甲基化可通过排除H2A.Z来影响染色质结构并影响基因沉默,而H2A.Z保护基因免受DNA甲基化的影响。

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