title: SRY (sex determining region Y)-box2 (Sox2)/poly ADP-ribose polymerase 1 (Parp1) complexes regulate pluripotency.
abstract: To gain insight into mechanisms controlling SRY (sex determining region Y)-box 2 (Sox2) protein activity in mouse embryonic stem cells (ESCs), the endogenous Sox2 gene was tagged with FLAG/Hemagglutinin (HA) sequences by homologous recombination. Sox2 protein complexes were purified from Sox2/FLAG/HA knockin ESCs, and interacting proteins were defined by mass spectrometry. One protein in the complex was poly ADP-ribose polymerase I (Parp1). The results presented below demonstrate that Parp1 regulates Sox2 protein activity. In response to fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling, Parp1 auto-poly ADP-ribosylation enhances Sox2-Parp1 interactions, and this complex inhibits Sox2 binding to octamer-binding transcription factor 4 (Oct4)/Sox2 enhancers. Based on these results, we propose a unique mechanism in which FGF signaling fine-tunes Sox2 activity through posttranslational modification of a critical interacting protein, Parp1, and balances the maintenance of ESC pluripotency and differentiation. In addition, we demonstrate that regulation of Sox2 activity by Parp1 is critical for efficient generation of induced pluripotent stem cells.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Yi-Shin
authors.initials: YS
authors.lastname: Lai
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Pawlik
authors.forename: Dewang
authors.initials: D
authors.lastname: Zhou
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Renfrow
authors.forename: Tim M
authors.initials: TM
authors.lastname: Townes
mesh_terms: D000244:Adenosine Diphosphate / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D018390:Gene Targeting; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008957:Models, Genetic; D039904:Pluripotent Stem Cells / Q000166:cytology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011995:Recombination, Genetic; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D000244:Adenosine Diphosphate; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases