Damt-1 Enhances Resistance To Hyperosmotic Through H3K27me3 In Caenorhabditis Elegans

N6-methyldeoxyadenine(6mA)is a main type of DNA methylation in bacteria.It represents part of a restricted modification system that can distinguish between the host genome and invader DNA.Recently,DNA 6mA has also been detected in some eukaryotes.In C.elegans,the DNA methyltransferase is DAMT-1,and the DNA demethylase is NMAD-1.Although studies have shown that DNA 6mA can be used as an epigenetic marker,its physiological function in eukaryotes remains unclear.Previous studies have reported that the genetic changes of DNA 5mC methylation are related to intergenerational inheritance in response to a high-fat diet,providing evidence that DNA methylation can be intergenerational.Subsequent studies have also reported that histone H3K4me3 and DNA 6mA modifications are necessary for the transfer of mitochondrial stress adaptiveness to progeny,thereby alleviating mitochondrial stress in progeny.These findings indicate that 6mA is an epigenetic marker that regulate the stress response and transmit intergenerational genetic signals in worms.Although these results confirms that histone methylation and DNA methylation are connected,the specific mechanism of action is not yet clear.In this study,we demonstrated that deletion of DNA 6mA methyltransferase gene damt-1 increased the resistance of worms to hypertonicity,which accompanied by an increase in the level of H3K27me3.In C.elegans,the methyltransferase of histone H3K27me3 is MES-2,and the demethylases include UTX-1,JMJD-3.1,JMJD-3.2,and JMJD-3.3.We found that silencing of utx-1 up-regulated the level of H3K27me3,enhancing resistance of worms to hypertonicity.These results implicated that down-regulation of damt-1 by hypertonicity probably lead to a decrease in utx-1 expression and an increase in the level of H3K27me3,thereby enhancing resistance of worms under hyperosmotic conditions.In addition,the mechanism of DNA hypermethylation resistance to hyperosmolarity could also be passed on to the offspring.We found that after the hypertonicity treatment in the parents,the ability to resist hypertonicity and the pathogens infected were enhanced in the offspring.Finally,we found that after hypertonicity treatment,induction of the expression of gpdh-1,which is crucial for hypertonicity resistance,is independent of damt-1.This study provides a novel mechanism underlying the resistance of C.elegans to hypertonicity.