title: The Pluripotency Factor NANOG Binds to GLI Proteins and Represses Hedgehog-mediated Transcription.
abstract: The Hedgehog (HH) signaling pathway is essential for the maintenance and response of several types of stem cells. To study the transcriptional response of stem cells to HH signaling, we searched for proteins binding to GLI proteins, the transcriptional effectors of the HH pathway in mouse embryonic stem (ES) cells. We found that both GLI3 and GLI1 bind to the pluripotency factor NANOG. The ectopic expression of NANOG inhibits GLI1-mediated transcriptional responses in a dose-dependent fashion. In differentiating ES cells, the presence of NANOG reduces the transcriptional response of cells to HH. Finally, we found thatGli1andNanogare co-expressed in ES cells at high levels. We propose that NANOG acts as a negative feedback component that provides stem cell-specific regulation of the HH pathway.
authors.affiliation: From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Lex
authors.affiliation: From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
authors.forename: HaeWon
authors.initials: H
authors.lastname: Chung
authors.affiliation: From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Giovanetti
authors.affiliation: Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Ji
authors.affiliation: Institute for Cellular and Molecular Biology, and Proteomics Facility, The University of Texas, Austin, Texas 78712 and.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Person
authors.affiliation: From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
authors.forename: Jonghwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and svokes@austin.utexas.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Vokes
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D041681:NIH 3T3 Cells; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D014158:Transcription, Genetic; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3
chemical_list: C498520:Gli1 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009419:Nerve Tissue Proteins; C465570:Shh protein, mouse; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3
keywords: GLI proteins; Hedgehog signaling pathway; Nanog; differentiation; embryonic stem cell; repressor; stem cells; transcription repressor