Loading...
Please wait, while we are loading the content...
Similar Documents
O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter
| Content Provider | Scilit |
|---|---|
| Author | Zhang, Zhen Costa, Flávia C. Tan, Ee Phie Bushue, Nathan DiTacchio, Luciano Costello, Catherine E. McComb, Mark E. Whelan, Stephen A. Peterson, Kenneth R. Slawson, Chad |
| Copyright Year | 2016 |
| Description | Journal: Journal of Biological Chemistry One mode of γ-globin gene silencing involves a GATA-1·FOG-1·Mi2β repressor complex that binds to the −566 GATA site relative to the$ ^{A}$γ-globin gene cap site. However, the mechanism of how this repressor complex is assembled at the −566 GATA site is unknown. In this study, we demonstrate that the O-linked N-acetylglucosamine (O-GlcNAc) processing enzymes, O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA), interact with the$ ^{A}$γ-globin promoter at the −566 GATA repressor site; however, mutation of the GATA site to GAGA significantly reduces OGT and OGA promoter interactions in β-globin locus yeast artificial chromosome (β-YAC) bone marrow cells. When WT β-YAC bone marrow cells are treated with the OGA inhibitor Thiamet-G, the occupancy of OGT, OGA, and Mi2β at the$ ^{A}$γ-globin promoter is increased. In addition, OGT and Mi2β recruitment is increased at the$ ^{A}$γ-globin promoter when γ-globin becomes repressed in postconception day E18 human β-YAC transgenic mouse fetal liver. Furthermore, we show that Mi2β is modified with O-GlcNAc, and both OGT and OGA interact with Mi2β, GATA-1, and FOG-1. Taken together, our data suggest that O-GlcNAcylation is a novel mechanism of γ-globin gene regulation mediated by modulating the assembly of the GATA-1·FOG-1·Mi2β repressor complex at the −566 GATA motif within the promoter. |
| Related Links | http://www.jbc.org/content/291/30/15628.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957047/pdf http://www.jbc.org/article/S002192582039699X/pdf |
| Ending Page | 15640 |
| Page Count | 13 |
| Starting Page | 15628 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m116.721928 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 30 |
| Volume Number | 291 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Gata Transcription Factor O-glcnac-transferase O-linked N-acetylglucosamine (o-glcnac) Post-translational Modification (ptm) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |