O-GlcNAc transferase regulates transcriptional activity of human Oct4
| Autor: | Jae-Min Lim, Lance Wells, Sandii Constable, Krithika Vaidyanathan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Glycosylation Cell N-Acetylglucosaminyltransferases Biochemistry Regular Manuscripts 03 medical and health sciences medicine Transcriptional regulation Transferase Humans Induced pluripotent stem cell Transcription factor Embryonic Stem Cells 030102 biochemistry & molecular biology Chemistry Promoter Embryonic stem cell Cell biology A-site 030104 developmental biology medicine.anatomical_structure HEK293 Cells Octamer Transcription Factor-3 Protein Processing Post-Translational |
| Popis: | O-linked β-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. |
| Databáze: | OpenAIRE |
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