O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter
| Autor: | Nathan Bushue, Zhen Zhang, Mark E. McComb, Luciano DiTacchio, Catherine E. Costello, Stephen A. Whelan, Chad Slawson, Ee Phie Tan, Kenneth R. Peterson, Flávia C. Costa |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Glycobiology and Extracellular Matrices Repressor Mice Transgenic Biology N-Acetylglucosaminyltransferases Response Elements Biochemistry Mice 03 medical and health sciences Transcription (biology) hemic and lymphatic diseases Animals Humans GATA1 Transcription Factor gamma-Globins Gene Silencing Globin Molecular Biology Gene Transcription factor Regulation of gene expression Nuclear Proteins Cell Biology Molecular biology beta-N-Acetylhexosaminidases 030104 developmental biology GATA transcription factor CHD4 K562 Cells Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 291:15628-15640 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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