linking metabolism to epigenetics through O-GlcNAcylation

JA Hanover, MW Krause, DC Love - Nature reviews Molecular cell …, 2012 - nature.com
JA Hanover, MW Krause, DC Love
Nature reviews Molecular cell biology, 2012nature.com
O-GlcNAcylation, which is a nutrient-sensitive sugar modification, participates in the
epigenetic regulation of gene expression. The enzymes involved in O-linked β-dN-
acetylglucosamine (O-GlcNAc) cycling–O-GlcNAc transferase (OGT) and O-GlcNAcase
(OGA)–target key transcriptional and epigenetic regulators including RNA polymerase II,
histones, histone deacetylase complexes and members of the Polycomb and Trithorax
groups. Thus, O-GlcNAc cycling may serve as a homeostatic mechanism linking nutrient …
Abstract
O-GlcNAcylation, which is a nutrient-sensitive sugar modification, participates in the epigenetic regulation of gene expression. The enzymes involved in O-linked β-D-N-acetylglucosamine (O-GlcNAc) cycling – O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) – target key transcriptional and epigenetic regulators including RNA polymerase II, histones, histone deacetylase complexes and members of the Polycomb and Trithorax groups. Thus, O-GlcNAc cycling may serve as a homeostatic mechanism linking nutrient availability to higher-order chromatin organization. In response to nutrient availability, O-GlcNAcylation is poised to influence X chromosome inactivation and genetic imprinting, as well as embryonic development. The wide range of physiological functions regulated by O-GlcNAc cycling suggests an unexplored nexus between epigenetic regulation in disease and nutrient availability.
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