A novel N6-Deoxyadenine methyltransferase METL-9 modulates C. elegans immunity via dichotomous mechanisms

Abstract

N6-Methyldeoxyadenine (6mA) has been rediscovered as a DNA modification with potential biological function in metazoans. However, the physiological function and regulatory mechanisms regarding the establishment, maintenance and removal of 6mA in eukaryotes are still poorly understood. Here we show that genomic 6mA levels change in response to pathogenic infection in Caenorhabditis elegans (C. elegans). We further identify METL-9 as the methyltransferase that catalyzes DNA 6mA modifications upon pathogen infection. Deficiency of METL-9 impairs the induction of innate immune response genes and renders the animals more susceptible to pathogen infection. Interestingly, METL-9 functions through both 6mA-dependent and -independent mechanisms to transcriptionally regulate innate immunity. Our findings reveal that 6mA is a functional DNA modification in immunomodulation in C. elegans.

6mA-METL-9 axis regulates innate immunity in C. elegans

“…The study by Ma et al 6 in Cell Research reported that 6mA levels in C. elegans gDNA increased greatly when the animals were infected by bacteria (Fig. 1).…”

“…N 6 -methyldeoxyadenosine (6mA) is well characterized as the most abundant DNA modification in many prokaryotes, regulating fundamental processes such as DNA transcription, replication, and repair. 1 Since 2015, high levels of 6mA were detected in the genomes of several lower eukaryotes with unique distribution patterns, suggesting regulatory roles of 6mA as an additional DNA mark in these systems.…”

Antibacterial activity of cinnamon essential oil and its main component of cinnamaldehyde and the underlying mechanism

“…Caenorhabditis elegans ( C. elegans ), characterized by its small size, short lifecycle, transparent body, suitability for large-scale genetic research and phenotype analysis, and sensitivity to various environmental exposures, has proven to be a robust invertebrate model for investigating host-pathogen interactions ( Martineau et al, 2021 ; Qu et al, 2023a ; Ma et al, 2023 ). Like other invertebrates, C. elegans relies entirely on its innate immune system to defend against pathogens.…”