Nutrient Regulation of Immunity: O-GlcNAcylation Regulates Stimulus-Specific NF-κB-Dependent Transcription

Nutrients regulate gene transcription by the dynamic cycling of O-linked N-acetylglucosamine (O-GlcNAc) on proteins that constitute the transcriptional machinery. A study shows that O-GlcNAcylation of the nuclear factor kappa B (NF-kappa B) subunit c-Rel is required for its binding to the promoters of some, but not all, key T cell receptor-dependent genes; however, O-GlcNAcylation is dispensable for the binding of c-Rel to the promoters of tumor necrosis factor-alpha-dependent genes. This study not only illustrates how specific stimuli that act on the same transcription factor can elicit the expression of particular sets of genes, it also suggests a possible mechanism for autoimmunity in diabetes.