CMT2 and CMT3 are two plant-specific DNA methylases. CMT2 mainly methylates CHH, while CMT3 methylates CHG. But how they are different? This research reveals that there are several mechanisms mark the CMT2/3 difference. 1. The key site for recognizing CHG in CMT2 has mutated, thereby reducing the CHG methylation ability and improving the CHH methylation ability; 2. CMT2 has a longer N-terminus than CMT3, which is long and disordered, reducing protein stability and is sensitive to high temperature, causing the protein to degrade at high temperatures and respond to the environment. In addition, it was found that CMT3 is an ancient form of CMT-type DNA methylases, which exists from algae to angiosperms. The CMT3 of charophytes and liverwort can partially or almost completely complement the Arabidopsis cmt3 mutant; CMT2 only exists in angiosperms and is derived from CMT3 through gene duplication and divergence. In flowering plants, the emergence of CMT2 may replace the loss of DNMT3 for heterochromatic CHH methylation.

Jiang, J., Gwee, J., Fang, J., Leichter, S.M., Sanders, D., Ji, X., Song, J. and Zhong, X., 2024. Substrate specificity and protein stability drive the divergence of plant-specific DNA methyltransferases. Science Advances, (in press).