Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3 K4 methylation in Arabidopsis thaliana,it is unknown whether and how these histo...Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3 K4 methylation in Arabidopsis thaliana,it is unknown whether and how these histone methyltransferases affect DNA methylation.Here,we found that the redundant ATX1-5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation.The expression and H3 K4 me3 levels of both RNAdirected DNA methylation(RdDM)genes(NRPE1,DCL3,IDN2,and IDP2)and active DNA demethylation genes(ROS1,DML2,and DML3)were downregulated in the atx1/2/4/5 mutant.Consistent with the facts that the active DNA demethylation pathway mediates DNA demethylation mainly at CG and CHG sites,and that the RdDM pathway mediates DNA methylation mainly at CHH sites,whole-genome DNA methylation analyses showed that hyper-CG and CHG DMRs in atx1/2/4/5 significantly overlapped with those in the DNA demethylation pathway mutant ros1 dml2 dml3(rdd),and that hypo-CHH DMRs in atx1/2/4/5 significantly overlapped with those in the RdDM mutant nrpe1,suggesting that the ATX paralogues function redundantly to regulate DNA methylation by promoting H3 K4 me3 levels and expression levels of both RdDM genes and active DNA demethylation genes.Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes,we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation.This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation.展开更多
基金the National Natural Science Foundation of China(32025003)by the National Key Research and Development Program of China(2016YFA0500801)from the Chinese Ministry of Science and Technology。
文摘Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3 K4 methylation in Arabidopsis thaliana,it is unknown whether and how these histone methyltransferases affect DNA methylation.Here,we found that the redundant ATX1-5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation.The expression and H3 K4 me3 levels of both RNAdirected DNA methylation(RdDM)genes(NRPE1,DCL3,IDN2,and IDP2)and active DNA demethylation genes(ROS1,DML2,and DML3)were downregulated in the atx1/2/4/5 mutant.Consistent with the facts that the active DNA demethylation pathway mediates DNA demethylation mainly at CG and CHG sites,and that the RdDM pathway mediates DNA methylation mainly at CHH sites,whole-genome DNA methylation analyses showed that hyper-CG and CHG DMRs in atx1/2/4/5 significantly overlapped with those in the DNA demethylation pathway mutant ros1 dml2 dml3(rdd),and that hypo-CHH DMRs in atx1/2/4/5 significantly overlapped with those in the RdDM mutant nrpe1,suggesting that the ATX paralogues function redundantly to regulate DNA methylation by promoting H3 K4 me3 levels and expression levels of both RdDM genes and active DNA demethylation genes.Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes,we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation.This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation.