SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells
| Title: | SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells |
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| Authors: | Samuel A Myers, Sailaja Peddada, Nilanjana Chatterjee, Tara Friedrich, Kiichrio Tomoda, Gregor Krings, Sean Thomas, Jason Maynard, Michael Broeker, Matthew Thomson, Katherine Pollard, Shinya Yamanaka, Alma L Burlingame, Barbara Panning |
| Source: | eLife, Vol 5 (2016) |
| Publisher Information: | eLife Sciences Publications Ltd, 2016. |
| Publication Year: | 2016 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | SOX2, O-GlcNAc, pluripotency, transcription factors, embryonic stem cells, electron transfer dissociation, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression. This change correlates with altered protein-protein interactions and genomic occupancy of the O-GlcNAc-deficient SOX2 compared to wild type. In addition, SOX2 O-GlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC self-renewal. These findings show that SOX2 activity is modulated by O-GlcNAc, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/10647; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.10647 |
| Access URL: | https://doaj.org/article/ae84465bec52469ebcfd18408aa1e172 |
| Accession Number: | edsdoj.84465bec52469ebcfd18408aa1e172 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.10647 |
| Published in: | eLife |
| Language: | English |