ELT‐2 promotes O‐GlcNAc transferase OGT‐1 expression to modulate Caenorhabditis elegans lifespan. Issue 12 (6th July 2020)

• Record Type: Journal Article
• Authors: Su, Liangping; Zhao, Tingting; Li, Hongyuan; Li, Hongmei; Su, Xin; Ba, Xueqing; Zhang, Yu; Huang, Baiqu; Lu, Jun; Li, Xiaoxue
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 12(2020)
• Page Start: 4898
• Page End: 4907
• Publication Date: 2020-07-06
• Subjects: Caenorhabditis elegans -- GATA factor ELT‐2 -- lifespan -- OGT‐1; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29817
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: 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. Abstract : Our findings show that GATA factor ELT‐2 activates OGT‐1 transcription via its direct binding of the ogt‐1 promoter. The decreased ELT‐2 expression in old age leads to the decrease of OGT‐1 expression, and thereby drives natural aging of Caenorhabditis elegans . These data identify the key role of GATA factors in promoting OGT activity to modulate the C. elegans lifespan.