MBD2 couples DNA methylation to transposable element silencing during male gametogenesis.

MBD2 couples DNA methylation to transposable element silencing during male gametogenesis.
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DOI:
10.1038/s41477-023-01599-3
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发表时间:
2024-01
期刊:
影响因子:
18
通讯作者:
Jacobsen, Steven E.
Jacobsen, Steven E.
中科院分区:
生物学1区
文献类型:
--
作者:
Wang, Shuya;Wang, Ming;Ichino, Lucia;Boone, Brandon A.;Zhong, Zhenhui;Papareddy, Ranjith K.;Lin, Evan K.;Yun, Jaewon;Feng, Suhua;Jacobsen, Steven E.

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DNA甲基化是转座因子(TE)沉默的重要组成部分,但甲基化导致转录抑制的机制仍然知之甚少。在这里,我们研究拟南芥甲基CpG结合域(MBD)蛋白MBD1,MBD2和MBD4,并显示MBD2作为TE阻遏物在雄性配子发生。MBD2结合含有高水平CG甲基化的染色质区域,并且MBD2在与其启动子连接时能够沉默FWA基因。MBD2的损失导致激活的TE在成熟花粉的营养细胞中的一个小的子集,而不影响DNA甲基化水平,表明MBD2介导的沉默作用严格下游的DNA甲基化。mbd2中的TE激活在mbd5 mbd6和adcp1突变体背景中变得更加显著,表明MBD2与其他沉默途径冗余地作用以抑制TE。总的来说,我们的研究确定MBD2作为甲基阅读器,其作用于DNA甲基化的下游以在雄性配子发生期间沉默TE。转座因子的增殖对基因组构成了相当大的威胁。一个以前未知的甲基阅读器,MBD2,在雄性配子发生过程中抑制转座因子。MBD2与其他沉默途径以高度冗余的方式起作用,一起保持基因组稳定性。
DNA methylation is an essential component of transposable element (TE) silencing, yet the mechanism by which methylation causes transcriptional repression remains poorly understood. Here we study the Arabidopsis thaliana Methyl-CpG Binding Domain (MBD) proteins MBD1, MBD2 and MBD4 and show that MBD2 acts as a TE repressor during male gametogenesis. MBD2 bound chromatin regions containing high levels of CG methylation, and MBD2 was capable of silencing the FWA gene when tethered to its promoter. MBD2 loss caused activation at a small subset of TEs in the vegetative cell of mature pollen without affecting DNA methylation levels, demonstrating that MBD2-mediated silencing acts strictly downstream of DNA methylation. TE activation in mbd2 became more significant in the mbd5 mbd6 and adcp1 mutant backgrounds, suggesting that MBD2 acts redundantly with other silencing pathways to repress TEs. Overall, our study identifies MBD2 as a methyl reader that acts downstream of DNA methylation to silence TEs during male gametogenesis. Transposable element proliferation poses considerable threats to genomes. A previously unknown methyl reader, MBD2, represses transposable elements during male gametogenesis. MBD2 acts with a high degree of redundancy with other silencing pathways, together preserving genome stability.
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