SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells
- University of California, San Francisco, United States
- Gladstone Institute University of California, San Francisco, United States
Abstract
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 modification, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor.
Article and author information
Author details
Reviewing Editor
- Kathrin Plath, University of California, Los Angeles, United States
Publication history
- Received: August 8, 2015
- Accepted: March 5, 2016
- Accepted Manuscript published: March 7, 2016 (version 1)
- Accepted Manuscript updated: March 22, 2016 (version 2)
- Version of Record published: April 19, 2016 (version 3)
Copyright
© 2016, Myers et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells
eLife 5:e10647.
https://doi.org/10.7554/eLife.10647
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