Glucose-induced expression of MIP-1 genes requires O-GlcNAc transferase in monocytes.
O-glycosylation has emerged as an important modification of nuclear proteins, and it appears to be involved in gene regulation. Recently, we have shown that one of the histone methyl transferases (MLL5) is activated through O-glycosylation by O-GlcNAc transferase (OGT). Addition of this monosaccharide is essential for forming a functional complex. However, in spite of the abundance of OGT in the nucleus, the impact of nuclear O-glycosylation by OGT remains largely unclear. To address this issue, the present study was undertaken to test the impact of nuclear O-glycosylation in a monocytic cell line, THP-1. Using a cytokine array, MIP-1alpha and -1beta genes were found to be regulated by nuclear O-glycosylation. Biochemical purification of the OGT interactants from THP-1 revealed that OGT is an associating partner for distinct co-regulatory complexes. OGT recruitment and protein O-glycosylation were observed at the MIP-1alpha gene promoter; however, the known OGT partner (HCF-1) was absent when the MIP-1alpha gene promoter was not activated. From these findings, we suggest that OGT could be a co-regulatory subunit shared by functionally distinct complexes supporting epigenetic regulation.
Chikanishi
Toshihiro
T
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Fujiki
Ryoji
R
Hashiba
Waka
W
Sekine
Hiroki
H
Yokoyama
Atsushi
A
Kato
Shigeaki
S
D002460:Cell Line; D054405:Chemokine CCL3 / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D009000:Monocytes / Q000201:enzymology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D054405:Chemokine CCL3; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D005947:Glucose