Dnmt1-independent CG methylation contributes to nucleosome positioning in diverse eukaryotes.

Dnmt1-independent CG methylation contributes to nucleosome positioning in diverse eukaryotes.
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DOI:
10.1016/j.cell.2014.01.029
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发表时间:
2014-03-13
期刊:
影响因子:
64.5
通讯作者:
Zilberman D
Zilberman D
中科院分区:
生物学1区
文献类型:
--
作者:
Huff JT;Zilberman D

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在许多真核生物中,DNMT1在表观遗传学上传播对称的CG甲基化。由于脱氨基甲基胞嘧啶的修复不完善,它们的基因组通常会耗尽CG二核苷酸。在这里,我们对缺乏Dnmt1的不同物种进行了广泛的调查,结果表明,令人惊讶的是,对称的CG甲基化仍然经常存在,这是由一个新的DNA甲基转移酶家族Dnmt5催化的。许多含有DNMT5的生物体在10亿多年前出现了聚集的甲基化,特别是在核小体连接子中。聚集性甲基化以前所未有的密度发生,并直接不利核小体,导致核小体在簇间定位。密集的甲基化是由一种新的基因组序列进化机制实现的,该机制丰富了CG二核苷酸,推动了已知的最高CG频率。具有连接子甲基化的物种具有小的、转录活性的核,接近染色质压缩的物理极限。这些特征构成了一个以前不为人知的基因组结构,其中密集的甲基化影响核小体位置,可能在极端空间限制下促进核过程。
Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides, because of imperfect repair of deaminated methylcytosines. Here, we extensively surveyed diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present, catalyzed by a novel DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged over a billion years ago exhibit clustered methylation specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a novel regime of genomic sequence evolution that enriches CG dinucleotides, driving the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints.
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