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.

胞嘧啶甲基化调节整个真核生物的基本基因组功能，但是基本的问题是核糖体还是裸露的DNA是植物和动物甲基转移酶的优选底物仍未解决。在这里，我们显示单个DDM1 / Lsh家族核小体重塑剂的遗传失活偏向拟南芥和小鼠中的核糖体间接头DNA的甲基化。我们发现DDM1可以使结合到核小体的DNA甲基化，这表明无核小体的DNA是体内真核甲基转移酶的优选底物。此外，我们显示拟南芥中DDM1和接头组蛋白H1同时突变再现了十亿年前与开花植物和动物不同的物种的特定于接头的强甲基化模式。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与DNA甲基化之间的联系来发展。