O-GlcNAc cycling: Emerging roles in development and epigenetics |
| |
| Authors: | Dona C Love Michael W Krause John A Hanover |
| |
| Institution: | 1. Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bldg 8 Rm B127, 8 Center Dr MSC 0850, NIH Bethesda, MD 20892-0850, United States;2. Laboratory of Molecular Biology, NIDDK, National Institutes of Health, United States;3. Department of Biochemistry and Molecular Biology;6. University of Kansas Cancer Center;4. Department of Neurology;5. University of Kansas Alzheimer''s Disease Center, University of Kansas Medical Center, Kansas City, Kansas 64108;1. Department of Biological Chemistry, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA;1. Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada;2. Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada;3. Department of Chemistry, University of York, York, YO10 5DD, England;1. Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06519, USA;2. Section of Comparative Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06519, USA;3. Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06519, USA;4. School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China;1. Department of Microbiology, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, United States;2. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, United States;1. MPI of Biochemistry, Chromatin and Chromosome Biology, Am Klopferspitz 18, 82152 Martinsried, Germany |
| |
| Abstract: | The nutrient-sensing hexosamine signaling pathway modulates the levels of O-linked N-acetylglucosamine (O-GlcNAc) on key targets impacting cellular signaling, protein turnover and gene expression. O-GlcNAc cycling may be deregulated in neurodegenerative disease, cancer, and diabetes. Studies in model organisms demonstrate that the O-GlcNAc transferase (OGT/Sxc) is essential for Polycomb group (PcG) repression of the homeotic genes, clusters of genes responsible for the adult body plan. Surprisingly, from flies to man, the O-GlcNAcase (OGA, MGEA5) gene is embedded within the NK cluster, the most evolutionarily ancient of three homeobox gene clusters regulated by PcG repression. PcG repression also plays a key role in maintaining stem cell identity, recruiting the DNA methyltransferase machinery for imprinting, and in X-chromosome inactivation. Intriguingly, the Ogt gene resides near the Xist locus in vertebrates and is subject to regulation by PcG-dependent X-inactivation. OGT is also an enzymatic component of the human dosage compensation complex. These ‘evo-devo’ relationships linking O-GlcNAc cycling to higher order chromatin structure provide insights into how nutrient availability may influence the epigenetic regulation of gene expression. O-GlcNAc cycling at promoters and PcG repression represent concrete mechanisms by which nutritional information may be transmitted across generations in the intra-uterine environment. Thus, the nutrient-sensing hexosamine signaling pathway may be a key contributor to the metabolic deregulation resulting from prenatal exposure to famine, or the ‘vicious cycle’ observed in children of mothers with type-2 diabetes and metabolic disease. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
