| Citation | Love DC, Ghosh S, Mondoux MA, Fukushige T, Wang P, Wilson MA, Iser WB, Wolkow CA, Krause MW, Hanover JA. Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity. Proc Natl Acad Sci U S A, 2010. |
| PubMed ID | 20368426 |
| Short Description | Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity. GEO Record: GSE18132 GSE18131 GSE18130 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00036090.ce.mr.csv |
| # of Conditions | 18 |
Full Description
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Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration. Experimental Details: WBPaper00036090:WT_Starved_L1_bio_rep1 WBPaper00036090:WT_Starved_L1_bio_rep2 WBPaper00036090:WT_Starved_L1_bio_rep3 WBPaper00036090:Ogt_starved_L1_bio_rep1 WBPaper00036090:Ogt_starved_L1_bio_rep2 WBPaper00036090:Ogt_starved_L1_bio_rep3 WBPaper00036090:Oga_starved_L1_bio_rep1 WBPaper00036090:Oga_starved_L1_bio_rep2 WBPaper00036090:Oga_starved_L1_bio_rep3 WBPaper00036090:WT_Fed_L4_bio_rep1 WBPaper00036090:WT_Fed_L4_bio_rep2 WBPaper00036090:WT_Fed_L4_bio_rep3 WBPaper00036090:Ogt_Fed_L4_bio_rep1 WBPaper00036090:Ogt_Fed_L4_bio_rep2 WBPaper00036090:Ogt_Fed_L4_bio_rep3 WBPaper00036090:Oga_Fed_L4_bio_rep1 WBPaper00036090:Oga_Fed_L4_bio_rep2 WBPaper00036090:Oga_Fed_L4_bio_rep3. |
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