title: Tgif1 Counterbalances the Activity of Core Pluripotency Factors in Mouse Embryonic Stem Cells.
abstract: Core pluripotency factors, such as Oct4, Sox2, and Nanog, play important roles in maintaining embryonic stem cell (ESC) identity by autoregulatory feedforward loops. Nevertheless, the mechanism that provides precise control of the levels of the ESC core factors without indefinite amplification has remained elusive. Here, we report the direct repression of core pluripotency factors by Tgif1, a previously known terminal repressor of TGFβ/activin/nodal signaling. Overexpression of Tgif1 reduces the levels of ESC core factors, whereas its depletion leads to the induction of the pluripotency factors. We confirm the existence of physical associations between Tgif1 and Oct4, Nanog, and HDAC1/2 and further show the level of Tgif1 is not significantly altered by treatment with an activator/inhibitor of the TGFβ/activin/nodal signaling. Collectively, our findings establish Tgif1 as an integral member of the core regulatory circuitry of mouse ESCs that counterbalances the levels of the core pluripotency factors in a TGFβ/activin/nodal-independent manner.
authors.affiliation: Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, the University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Bum-Kyu
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, the University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Jiwoon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, the University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rhee
authors.affiliation: Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, the University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Haewon
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Kun-Yong
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.affiliation: Department of Molecular Biosciences, the University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, the University of Texas at Austin, Austin, TX 78712, USA. Electronic address: jonghwankim@mail.utexas.edu.
authors.forename: Jonghwan
authors.initials: J
authors.lastname: Kim
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism; D004622:Embryo, Mammalian; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C490797:Tgif1 protein, mouse; D016212:Transforming Growth Factor beta; D028341:Activins; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2