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Updated: Apr 21, 2026
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
O-GlcNAc and the epigenetic regulation of gene expression
Brian A Lewis1, John A Hanover2
1From the NCI and lewisbri@mail.nih.gov.
Abstract:
O-GlcNAcylation is an abundant nutrient-driven modification linked to cellular signaling and regulation of gene expression. Utilizing precursors derived from metabolic flux, O-GlcNAc functions as a homeostatic regulator. The enzymes of O-GlcNAc cycling, OGT and O-GlcNAcase, act in mitochondria, the cytoplasm, and the nucleus in association with epigenetic "writers" and "erasers" of the histone code. Both O-GlcNAc and O-phosphate modify repeats within the RNA polymerase II C-terminal domain (CTD). By communicating with the histone and CTD codes, O-GlcNAc cycling provides a link between cellular metabolic status and the epigenetic machinery. Thus, O-GlcNAcylation is poised to influence trans-generational epigenetic inheritance.
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