title: SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells.
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, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.|Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, United States.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Myers
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Peddada
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Gladstone Institute University of California, San Francisco, San Francisco, United States.
authors.forename: Tara
authors.initials: T
authors.lastname: Friedrich
authors.affiliation: Gladstone Institute University of California, San Francisco, San Francisco, United States.
authors.forename: Kiichrio
authors.initials: K
authors.lastname: Tomoda
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, United States.
authors.forename: Gregor
authors.initials: G
authors.lastname: Krings
authors.affiliation: Gladstone Institute University of California, San Francisco, San Francisco, United States.
authors.forename: Sean
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Maynard
authors.affiliation: Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Broeker
authors.affiliation: Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Thomson
authors.affiliation: Gladstone Institute University of California, San Francisco, San Francisco, United States.|Institute for Human Genetics, Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Pollard
authors.affiliation: Gladstone Institute University of California, San Francisco, San Francisco, United States.|Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0002-8301-1172
authors.initials: B
authors.lastname: Panning
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D051379:Mice; D039904:Pluripotent Stem Cells / Q000502:physiology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
chemical_list: D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D000117:Acetylglucosamine
keywords: O-GlcNAc; SOX2; biochemistry; developmental biology; electron transfer dissociation; embryonic stem cells; mouse; pluripotency; stem cells; transcription factors