Genome-wide negative feedback drives transgenerational DNA methylation dynamics in Arabidopsis.
Genome-wide negative feedback drives transgenerational DNA methylation dynamics in Arabidopsis.
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DOI：
10.1371/journal.pgen.1005154
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发表时间：
2015-04
期刊：
影响因子：
4.5
通讯作者：
Kakutani T
中科院分区：
文献类型：
--
作者：
Ito T;Tarutani Y;To TK;Kassam M;Duvernois-Berthet E;Cortijo S;Takashima K;Saze H;Toyoda A;Fujiyama A;Colot V;Kakutani T
表型的表观遗传变异，特别是与DNA甲基化相关的表观遗传变异，通常在植物中遗传多代。活性和非活性染色质状态是可遗传的，并且可以通过正反馈以跨代方式维持甚至放大。然而，控制跨代DNA甲基化动态的机制在很大程度上是未知的。作为了解跨代动态的一种方法，我们通过全基因组DNA甲基化测序研究了拟南芥染色质重塑基因DDM1（DNA甲基化减少1）突变体中受损DNA甲基化的长期影响。ddm 1突变诱导转座因子（TE）的DNA甲基化急剧减少，并在初始世代中重复，同时还诱导数百个位点的异位DNA甲基化。出乎意料的是，这种异位甲基化只有在反复自花授粉后才能看到。异位胞嘧啶甲基化主要在非CG背景下发现，并且从转录单位内的3'区域开始并向上游扩散。值得注意的是，当染色体与DNA甲基化减少从ddm 1突变体引入到DDM 1野生型背景，ddm 1衍生的染色体也诱导类似的从头积累的DNA甲基化的反式。这些结果使我们提出了一个模型来解释跨代DNA甲基化再分配的全基因组负反馈。全局负反馈与局部正反馈一起将确保基因组内染色质状态的稳健和平衡的分化。DNA甲基化对于控制转座因子和基因的活性是重要的。DNA甲基化在植物中的一个有趣的特征是，它的模式可以以孟德尔的方式在多代中以高保真度遗传。然而，控制跨代DNA甲基化动态的机制在很大程度上是未知的。拟南芥的染色质重塑基因DDM1（DNA甲基化减少1）突变体显示出转座子和重复序列中DNA甲基化的急剧减少，并且在通过自花授粉的繁殖过程中也显示出发育表型的渐进变化。我们现在使用全基因组DNA甲基化测序表明，在重复自交后，ddm 1突变诱导了数百个基因座DNA甲基化的异位积累。值得注意的是，即使在野生型背景中，DNA甲基化的类似从头增加也可以由具有降低的DNA甲基化的染色体反式诱导。总的来说，我们的研究结果支持一个模型来解释跨代DNA甲基化再分配的全基因组负反馈，这应该是重要的基因组内的DNA甲基化状态的平衡分化。
Epigenetic variations of phenotypes, especially those associated with DNA methylation, are often inherited over multiple generations in plants. The active and inactive chromatin states are heritable and can be maintained or even be amplified by positive feedback in a transgenerational manner. However, mechanisms controlling the transgenerational DNA methylation dynamics are largely unknown. As an approach to understand the transgenerational dynamics, we examined long-term effect of impaired DNA methylation in Arabidopsis mutants of the chromatin remodeler gene DDM1 (Decrease in DNA Methylation 1) through whole genome DNA methylation sequencing. The ddm1 mutation induces a drastic decrease in DNA methylation of transposable elements (TEs) and repeats in the initial generation, while also inducing ectopic DNA methylation at hundreds of loci. Unexpectedly, this ectopic methylation can only be seen after repeated self-pollination. The ectopic cytosine methylation is found primarily in the non-CG context and starts from 3’ regions within transcription units and spreads upstream. Remarkably, when chromosomes with reduced DNA methylation were introduced from a ddm1 mutant into a DDM1 wild-type background, the ddm1-derived chromosomes also induced analogous de novo accumulation of DNA methylation in trans. These results lead us to propose a model to explain the transgenerational DNA methylation redistribution by genome-wide negative feedback. The global negative feedback, together with local positive feedback, would ensure robust and balanced differentiation of chromatin states within the genome. DNA methylation is important for controlling activity of transposable elements and genes. An intriguing feature of DNA methylation in plants is that its pattern can be inherited over multiple generations at high fidelity in a Mendelian manner. However, mechanisms controlling the trans-generational DNA methylation dynamics are largely unknown. Arabidopsis mutants of a chromatin remodeler gene DDM1 (Decrease in DNA Methylation 1) show drastic reduction of DNA methylation in transposons and repeats, and also show progressive changes in developmental phenotypes during propagation through self-pollination. We now show using whole genome DNA methylation sequencing that upon repeated selfing, the ddm1 mutation induces an ectopic accumulation of DNA methylation at hundreds of loci. Remarkably, even in the wild type background, the analogous de novo increase of DNA methylation can be induced in trans by chromosomes with reduced DNA methylation. Collectively, our findings support a model to explain the transgenerational DNA methylation redistribution by genome-wide negative feedback, which should be important for balanced differentiation of DNA methylation states within the genome.
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DOI：
10.1073/pnas.1201043109
发表时间：
2012-02-28
影响因子：
11.1
作者：
Greaves, Ian K.;Groszmann, Michael;Dennis, Elizabeth S.
通讯作者：
Dennis, Elizabeth S.
影响因子：
56.9
作者：
Jacobsen, SE;Meyerowitz, EM
通讯作者：
Meyerowitz, EM
影响因子：
4.5
作者：
Henderson IR;Deleris A;Wong W;Zhong X;Chin HG;Horwitz GA;Kelly KA;Pradhan S;Jacobsen SE
通讯作者：
Jacobsen SE
DOI：
10.1073/pnas.1212955109
发表时间：
2012-10-02
影响因子：
11.1
作者：
Colome-Tatche, Maria;Cortijo, Sandra;Johannes, Frank
通讯作者：
Johannes, Frank
影响因子：
4.5
作者：
Coleman-Derr D;Zilberman D
通讯作者：
Zilberman D