Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation

Significance Plant SUVH family H3K9 methyltransferases play a key role in connecting the two epigenetic silencing marks, DNA methylation and H3K9me2. However, the regulation of SUVH protein activities and their precise role in the regulation of DNA methylation remains unclear. In this research, we performed a comprehensive investigation into the structure, biochemistry, and in vivo targeting characteristics of SUVH histone methyltransferases. For binding methylated DNA, we reveal that the SUVH family proteins possess a unique thumb loop-dependent base-flipping mechanism. For methyltransferase function, we reveal that SUVH6 is regulated by a dynamic autoinhibitory domain. Finally, our in vitro DNA-binding assays combined with ChIP-seq data uncover mechanisms to help explain context-biased non-CG DNA methylation in plants.