Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell. 2014 Mar 13;156(6):1286-1297. doi: 10.1016/j.cell.2014.01.029.
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 survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than 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 regime of genomic sequence evolution that enriches CG dinucleotides and drives 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.
Dnmt1 在后生动物中通过表观遗传方式复制 CG 二核苷酸的对称甲基化。由于脱氨基甲基胞嘧啶的不完全修复，它们的基因组通常缺乏 CG 二核苷酸。在这里，我们广泛调查了缺乏 Dnmt1 的多种物种，令人惊讶的是，尽管如此，CG 二核苷酸的对称甲基化仍然经常存在，并由另一种 DNA 甲基转移酶家族 Dnmt5 催化。在超过十亿年前就已经分化的许多含有 Dnmt5 的生物体中，存在着簇状甲基化，特别是在核小体连接区。簇状甲基化发生在前所未有的密度，并直接不利于核小体，有助于在簇之间进行核小体定位。密集的甲基化是由基因组序列进化的一种机制所驱动的，这种机制丰富了 CG 二核苷酸，并导致了已知的最高 CG 频率。具有连接子甲基化的物种具有小的、转录活跃的核，接近染色质紧缩的物理极限。这些特征构成了一种以前未被认识到的基因组结构，其中密集的甲基化影响核小体的位置，可能有助于在极端空间限制下的核过程。
