DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.
DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.
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DOI：
10.1101/gad.270876.115
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发表时间：
2015-10-15
影响因子：
10.5
通讯作者：
Henderson IR
中科院分区：
文献类型：
--
作者：
Yelina NE;Lambing C;Hardcastle TJ;Zhao X;Santos B;Henderson IR
Yelina等人表明，RNA指导的DNA甲基化足以局部沉默拟南芥常染色质交换热点，并与核小体密度和H3K9me2增加相关。这项工作表明，DNA甲基化起着关键作用，在建立结构域的减数分裂重组沿着染色体。在减数分裂过程中，同源染色体进行交叉重组，这通常集中在由遗传和表观遗传信息控制的狭窄热点。拟南芥染色体的重复着丝粒DNA高度甲基化，这也是交叉抑制。在这里，我们证明，RNA指导的DNA甲基化是足够的本地沉默拟南芥常染色质交换热点，并与核小体密度和H3K9me2增加。然而，CG DNA甲基化的损失met1触发表观遗传交叉重塑在染色体规模，与近着丝粒减少和常染色质增加重组。我们使用改变干扰和非干扰交叉修复途径（fancm和zip4）的重组突变体来证明重塑主要涉及干扰交叉的重新分布。使用全基因组亚硫酸氢盐测序，我们表明，交叉重塑是由着丝粒区域内的CG甲基化损失驱动的。使用细胞遗传学，我们分析了减数分裂DNA双链断裂（DSB）灶的met1，发现它们相对于野生型不变。我们建议，met1染色体结构被改变，导致着丝粒近端DSB被抑制成熟到干扰交叉。这些数据表明，DNA甲基化足以沉默交叉热点，并在建立减数分裂重组结构域沿着染色体发挥关键作用。
Yelina et al. show that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. This work demonstrates that DNA methylation plays a key role in establishing domains of meiotic recombination along chromosomes. During meiosis, homologous chromosomes undergo crossover recombination, which is typically concentrated in narrow hot spots that are controlled by genetic and epigenetic information. Arabidopsis chromosomes are highly DNA methylated in the repetitive centromeres, which are also crossover-suppressed. Here we demonstrate that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. However, loss of CG DNA methylation maintenance in met1 triggers epigenetic crossover remodeling at the chromosome scale, with pericentromeric decreases and euchromatic increases in recombination. We used recombination mutants that alter interfering and noninterfering crossover repair pathways (fancm and zip4) to demonstrate that remodeling primarily involves redistribution of interfering crossovers. Using whole-genome bisulfite sequencing, we show that crossover remodeling is driven by loss of CG methylation within the centromeric regions. Using cytogenetics, we profiled meiotic DNA double-strand break (DSB) foci in met1 and found them unchanged relative to wild type. We propose that met1 chromosome structure is altered, causing centromere-proximal DSBs to be inhibited from maturation into interfering crossovers. These data demonstrate that DNA methylation is sufficient to silence crossover hot spots and plays a key role in establishing domains of meiotic recombination along chromosomes.