O-GlcNAc transferase (OGT) is the enzyme catalyzing protein O-GlcNAcylation by addition of a single O-linked-β-N-acetylglucosamine molecule (O-GlcNAc) to nuclear and cytoplasmic targets, and it uses uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) as a donor. As UDP-GlcNAc is the final product of the nutrient-sensing hexosamine signaling pathway, overexpression or knockout of ogt in mammals or invertebrate models influences cellular nutrient-response signals and increases susceptibility to chronic diseases of aging. Evidence shows that OGT expression levels decrease in tissues of older mice and rats. However, how OGT expression is modulated in the aging process remains poorly understood. In Caenorhabditis elegans, the exclusive mammalian OGT ortholog OGT-1 is crucial for lifespan control. Here, we observe that worm OGT-1 expression gradually reduces during aging. By combining prediction via the "MATCH" algorithm and luciferase reporter assays, GATA factor ELT-2, the homolog of human GATA4, is identified as a transcriptional factor driving OGT-1 expression. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assays show ELT-2 directly binds to and activates the ogt-1 promoter. Knockdown of elt-2 decreases the global O-GlcNAc modification level and reduces the lifespan of wild-type worms. The reduction in lifespan caused by elt-2 RNA interference is abrogated by the loss of ogt-1. These results imply that GATA factors are able to activate OGT expression, which could be beneficial for longevity and the development of therapeutic treatment for aging-related diseases.

Caenorhabditis elegans NRF (NF-E2-related factor)/CNC (Cap'n'collar) transcription factor, Skinhead-1 (SKN-1), is conservatively critical for promoting phase II detoxification gene expressions in response to oxidative stress. SKN-1 activity is controlled by well-known phosphorylation and recently-reported O-GlcNAcylation. Whether other kinds of posttanslational modifications of SKN-1 occur and influence its function remains elusive. Here, we found arginines 484 and 516 (R484/R516) of SKN-1 were asymmetrically dimethylated by PRMT-1. Oxidative stress enhanced the binding of PRMT-1 to SKN-1. Consequently, asymmetrical dimethylation of arginines on SKN-1 was elevated. Loss of prmt-1 or disruption of R484/R516 dimethylation decreased the enrichment of SKN1 on the promoters of SKN-1-driven phase II detoxification genes, including gamma-glutamine cysteine synthetase gcs-1, glutathione S-transferases gst-7 and gst-4, which resulted in reduced ability of worms to defense against oxidative stress. These findings have important implications for investigating the physiological and pathological functions of arginine methylation on conserved NRF/CNC transcription factors in human diseases related to oxidative stress response.