O-GlcNAc transferase regulates transcriptional activity of human Oct4

被引:37
作者
Constable, Sandii [1 ,2 ,4 ]
Lim, Jae-Min [1 ,2 ,3 ]
Vaidyanathan, Krithika [1 ,2 ]
Wells, Lance [1 ,2 ]
机构
[1] Univ Georgia, Complex Carbohydrate Res Ctr, 315 Riverbend Rd, Athens, GA 30602 USA
[2] Univ Georgia, Dept Biochem & Mol Biol, 315 Riverbend Rd, Athens, GA 30602 USA
[3] Changwon Natl Univ, Dept Chem, Chang Won 641773, Gyeongnam, South Korea
[4] Emory Univ, Dept Human Genet, 615 Michael St, Atlanta, GA 30322 USA
基金
新加坡国家研究基金会;
关键词
Oct4; OGT; O-GlcNAc; transcription factor; EMBRYONIC STEM-CELLS; LINKED N-ACETYLGLUCOSAMINE; POU DOMAIN; INSULIN-RESISTANCE; SELF-RENEWAL; DNA-BINDING; NUCLEOCYTOPLASMIC GLYCOSYLATION; INTERACTION NETWORK; CYTOSOLIC PROTEINS; DYNAMIC INTERPLAY;
D O I
10.1093/glycob/cwx055
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
O-linked beta-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc. Octamer-binding protein 4 (Oct4) is one of the key transcription factors required for pluripotency of ES cells and more recently, the generation of induced pluripotent stem (iPS) cells. The action of Oct4 is modulated by the addition of several post-translational modifications, including O-GlcNAc. Previous studies in mice found a single site of O-GlcNAc addition responsible for transcriptional regulation. This study was designed to determine if this mechanism is conserved in humans. We mapped 10 novel sites of O-GlcNAc attachment on human Oct4, and confirmed a role for OGT in transcriptional activation of Oct4 at a site distinct from that found in mouse that allows distinction between different Oct4 target promoters. Additionally, we uncovered a potential new role for OGT that does not include its catalytic function. These results confirm that human Oct4 activity is being regulated by OGT by a mechanism that is distinct from mouse Oct4.
引用
收藏
页码:927 / 937
页数:11
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