| Title : O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the nonspecific lethal protein NSL3 - Wu_2017_J.Biol.Chem_292_10014 |
| Author(s) : Wu D , Zhao L , Feng Z , Yu C , Ding J , Wang L , Wang F , Liu D , Zhu H , Xing F , Conaway JW , Conaway RC , Cai Y , Jin J |
| Ref : Journal of Biological Chemistry , 292 :10014 , 2017 |
| 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 (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, OGT1(C964A), 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. |
| ESTHER : Wu_2017_J.Biol.Chem_292_10014 |
| PubMedSearch : Wu_2017_J.Biol.Chem_292_10014 |
| PubMedID: 28450392 |
| Gene_locus related to this paper: human-KANSL3 |
| Gene_locus related to this paper: human-KANSL3 |
Wu D, Zhao L, Feng Z, Yu C, Ding J, Wang L, Wang F, Liu D, Zhu H, Xing F, Conaway JW, Conaway RC, Cai Y, Jin J (2017)
O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the nonspecific lethal protein NSL3
Journal of Biological Chemistry
292 :10014
Wu D, Zhao L, Feng Z, Yu C, Ding J, Wang L, Wang F, Liu D, Zhu H, Xing F, Conaway JW, Conaway RC, Cai Y, Jin J (2017)
Journal of Biological Chemistry
292 :10014