Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation

Akan, Ilhan; Love, Dona C.; Harwood, Katryn R.; Bond, Michelle; Hanover, John A.

doi:10.1074/jbc.m115.704783

Cited by 37 publications

(47 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though this Review has generally focused on studies performed in mammalian systems, valuable insights have also been gained from significant efforts to characterize the role of O -GlcNAcylation in other model organisms, including C. elegans, Drosophila , and Arabidopsis 49, 69, 97–101 . Like those in mammalian systems, studies in these organisms have demonstrated the importance of O -GlcNAc signalling in the regulation of diverse cellular processes such as autophagy 102, 103 , circadian rhythm 104–106 , epigenetics 69, 97, 107 , carbohydrate and lipid metabolism 91, 92 , hormone signalling 106, 108 , protein homeostasis 109, 110 , and stress response 111, 112 . Thus, it is likely that the need for a robust biological system to regulate these vital cellular pathways in a coordinated and integrated fashion contributed to the evolutionary conservation of O -GlcNAcylation.…”

Section: Discussionmentioning

confidence: 99%

Protein O-GlcNAcylation: emerging mechanisms and functions

Yang

Qian

2017

Nat Rev Mol Cell Biol

821

869

View full text Add to dashboard Cite

O-GlcNAcylation—the attachment of O-linked N-acetylglucosamine (O-GlcNAc) moieties to cytoplasmic, nuclear and mitochondrial proteins—is a post-translational modification that regulates fundamental cellular processes in metazoans. A single pair of enzymes—O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)—controls the dynamic cycling of this post-translational modification in a nutrient- and stress-responsive manner. Recent years have seen remarkable advances in our understanding of O-GlcNAcylation at levels ranging from structural and molecular biology to cell signalling and gene regulation to physiology and disease. Emerging from these recent developments are new mechanisms and functions of O-GlcNAcylation that enable us to begin constructing a unified conceptual framework through which to understand the significance of this modification in cellular and organismal physiology.

show abstract

Section: Discussionmentioning

confidence: 99%

Protein O-GlcNAcylation: emerging mechanisms and functions

Yang

Qian

2017

Nat Rev Mol Cell Biol

821

869

View full text Add to dashboard Cite

show abstract

“…It also became clear that progress in this area required molecular identification of the enzymatic machinery carrying out O-GlcNAc addition and removal. In fly, OGT was identified as an orphan homeotic gene (Super Sex Combs) or sxc and shown to be involved in the epigenetic process of polycomb suppression [16,17]; the Oga gene was linked to trithorax transcriptional activation [18]. The first cloning of a nucleoporin (Nup62) [8] provided the molecular identity of an important substrate that was O-GlcNAc modified and fueled efforts to identify the enzymes involved.…”

Section: A Brief Historical Perspectivementioning

confidence: 99%

“…1). It is also clear that O-GlcNAc cycling plays an essential role in polycomb repression [16,17,25,26] and trithorax activation [18,25,27] which act to define and shape early fate decisions. It is also clear that O-GlcNAc cycling plays an essential role in polycomb repression [16,17,25,26] and trithorax activation [18,25,27] which act to define and shape early fate decisions.…”

Section: O-glcnac In Stem Cell Maintenance and Differentiationmentioning

confidence: 99%

“…Meanwhile in the fly and mouse, studies suggested that OGT was an essential enzyme. In fly, OGT was identified as an orphan homeotic gene (Super Sex Combs) or sxc and shown to be involved in the epigenetic process of polycomb suppression [16,17]; the Oga gene was linked to trithorax transcriptional activation [18]. In mice OGT deletion was linked to early embryonic lethality [19].…”

Section: A Brief Historical Perspectivementioning

confidence: 99%

See 1 more Smart Citation

T cell development and the physiological role of O‐GlcNAc

Abramowitz

Hanover

2018

FEBS Letters

Self Cite

View full text Add to dashboard Cite

O-GlcNAcylation is an essential post-translational modification important for integrating metabolism with cell physiology. Using diverse model systems, studies of this evolutionarily conserved intracellular glycosylation have highlighted its role in stem cell maintenance, lineage specification, and disease. Although discovered over 30 years ago, the study of O-GlcNAc continues to evolve and uncover surprising roles for O-GlcNAc and the enzymes of O-GlcNAc cycling: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In this review, using the immune system as a model of stem cell biology and cell fate determination, we discuss how O-GlcNAc is at the nexus of metabolism, proliferation, and disease.

show abstract

“…O-GlcNAcylation is part of the histone code, and histones are O-GlcNAcylated under diverse cellular conditions (28 -30). A recent study suggests that O-GlcNAc cycling also plays an important role in maintaining the epigenetic machinery in Drosophila (31). The RNA Pol II C-terminal domain (CTD) is modified by O-GlcNAc (32), facilitating preinitiation complex formation (33).…”

mentioning

confidence: 99%

O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter

Zhang

Costa²,

Tan

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

One mode of ␥-globin gene silencing involves a GATA-1⅐FOG-1⅐Mi2␤ repressor complex that binds to the ؊566 GATA site relative to the A ␥-globin gene cap site. However, the mechanism of how this repressor complex is assembled at the ؊566 GATA site is unknown. In this study, we demonstrate that the O-linked N-acetylglucosamine (O-GlcNAc) processing enzymes, O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA), interact with the A ␥-globin promoter at the ؊566 GATA repressor site; however, mutation of the GATA site to GAGA significantly reduces OGT and OGA promoter interactions in ␤-globin locus yeast artificial chromosome (␤-YAC) bone marrow cells. When WT ␤-YAC bone marrow cells are treated with the OGA inhibitor Thiamet-G, the occupancy of OGT, OGA, and Mi2␤ at the A ␥-globin promoter is increased. In addition, OGT and Mi2␤ recruitment is increased at the A ␥-globin promoter when ␥-globin becomes repressed in postconception day E18 human ␤-YAC transgenic mouse fetal liver. Furthermore, we show that Mi2␤ is modified with O-GlcNAc, and both OGT and OGA interact with Mi2␤, GATA-1, and FOG-1. Taken together, our data suggest that O-GlcNAcylation is a novel mechanism of ␥-globin gene regulation mediated by modulating the assembly of the GATA-1⅐FOG-1⅐Mi2␤ repressor complex at the ؊566 GATA motif within the promoter.

show abstract

Drosophila O-GlcNAcase Deletion Globally Perturbs Chromatin O-GlcNAcylation

Abstract: Gene expression during

Cited by 37 publications

References 55 publications

Protein O-GlcNAcylation: emerging mechanisms and functions

Protein O-GlcNAcylation: emerging mechanisms and functions

T cell development and the physiological role of O‐GlcNAc

O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter

Contact Info

Product

Resources

About