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タイトル: | SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells |
著者: | Myers, Samuel A. Peddada, Sailaja Chatterjee, Nilanjana Friedrich, Tara Tomoda, Kiichrio Krings, Gregor Thomas, Sean Maynard, Jason Broeker, Michael Thomson, Matthew Pollard, Katherine Yamanaka, Shinya Burlingame, Alma L. Panning, Barbara |
著者名の別形: | 山中, 伸弥 |
発行日: | 7-Mar-2016 |
出版者: | eLife Sciences Publications Ltd |
誌名: | eLife |
巻: | 5 |
論文番号: | e10647 |
抄録: | 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 OGlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC selfrenewal. These findings show that SOX2 activity is modulated by O-GlcNAc, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor. |
著作権等: | Copyright Myers et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
URI: | http://hdl.handle.net/2433/218635 |
DOI(出版社版): | 10.7554/eLife.10647 |
PubMed ID: | 26949256 |
出現コレクション: | 学術雑誌掲載論文等 |
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