Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation

被引:333
作者
Hanover, John A. [1 ]
Krause, Michael W. [2 ]
Love, Dona C. [1 ]
机构
[1] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA
[2] NIDDK, Mol Biol Lab, NIH, Bethesda, MD USA
关键词
EMBRYONIC STEM-CELLS; LINKED GLCNAC TRANSFERASE; BETA-N-ACETYLGLUCOSAMINIDASE; THRIFTY PHENOTYPE HYPOTHESIS; POLYCOMB GROUP GENES; INSULIN-RESISTANCE; CAENORHABDITIS-ELEGANS; TETRATRICOPEPTIDE REPEATS; DROSOPHILA-MELANOGASTER; PROTEIN GLYCOSYLATION;
D O I
10.1038/nrm3334
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
O-GlcNAcylation, which is a nutrient-sensitive sugar modification, participates in the epigenetic regulation of gene expression. The enzymes involved in O-linked beta-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.
引用
收藏
页码:312 / 321
页数:10
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