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DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
eLife ( IF 7.7 ) Pub Date : 2017-11-15 , DOI: 10.7554/elife.30674
David B Lyons 1 , Daniel Zilberman 1, 2
Affiliation  

Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation.

中文翻译:

DDM1 和 Lsh 重塑剂允许包裹在核小体中的 DNA 甲基化

胞嘧啶甲基化调节真核生物的基本基因组功能,但核小体还是裸 DNA 是植物和动物甲基转移酶的首选底物的基本问题仍未解决。在这里,我们表明单个 DDM1/Lsh 家族核小体重塑剂的遗传失活使拟南芥和小鼠的核小体间接头 DNA 甲基化偏向于甲基化。我们发现 DDM1 能够使与核小体结合的 DNA 甲基化,这表明无核小体的 DNA 是体内真核生物甲基转移酶的首选底物。此外,我们表明,拟南芥中 DDM1 和接头组蛋白 H1 的同时突变再现了十亿多年前从开花植物和动物分化出来的物种的强接头特异性甲基化模式。我们的结果表明,在没有重塑的情况下,核小体是 DNA 甲基转移酶的强大屏障。接头特异性甲基化可以简单地通过打破核小体重塑和 DNA 甲基化之间的联系来进化。
更新日期:2017-11-15
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