Title : O-Linked
N-acetylglucosamine transferase 1 1 regulates global
histone H4 acetylation via stabilization of the nonspecific lethal protein
NSL3
Abstract :
- The human males absent on the first ( MOF )-containing histone acetyltransferase nonspecific lethal ( NSL ) complex comprises nine subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase , isoform 1 1 (OGT1)
- However, whether the O-GlcNAc transferase activity of OGT1 controls histone acetyltransferase activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remain unclear
- Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4 Lys-16, Lys-5, and Lys-8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3
- Knocking down or overexpressing OGT1 in human cells remarkably affected the global acetylation of histone H4 residues Lys-16, Lys-5, and Lys-8
- Because OGT1 is a subunit of the NSL complex, we also investigated the function of OGT1 in this complex
- Co-transfection/co-immunoprecipitation experiments combined with in vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O-GlcNAcylates NSL3
- In addition, wheat germ agglutinin affinity purification verified the occurrence of O-GlcNAc modification on NSL3 in cells
- Moreover, O-GlcNAcylation of NSL3 by wild-type OGT1 (OGT1-WT) stabilized NSL3
- This stabilization was lost after co-transfection of NSL3 with an OGT1 mutant, OGT1C964A, that lacks O-GlcNAc transferase activity
- Furthermore, stabilization of NSL3 by OGT1-WT significantly increased the global acetylation levels of H4 Lys-5, Lys-8, and Lys-16 in cells
- These results suggest that OGT1 regulates the activity of the NSL complex by stabilizing NSL3