The pluripotency factor NANOG binds to GLI proteins and represses hedgehog-mediated transcription

Qiang Li; Rachel K. Lex; Haewon Chung; Simone M. Giovanetti; Zhicheng Ji; Hongkai Ji; Maria D. Person; Jonghwan Kim; Steven A. Vokes

doi:10.1074/jbc.M116.714857

The pluripotency factor NANOG binds to GLI proteins and represses hedgehog-mediated transcription

Qiang Li, Rachel K. Lex, Haewon Chung, Simone M. Giovanetti, Zhicheng Ji, Hongkai Ji, Maria D. Person, Jonghwan Kim, Steven A. Vokes

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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 toHHsignaling, 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 that Gli1 and Nanog are 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.

Original language	English (US)
Pages (from-to)	7171-7182
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	291
Issue number	13
DOIs	https://doi.org/10.1074/jbc.M116.714857
State	Published - Mar 25 2016

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1074/jbc.M116.714857

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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 toHHsignaling, 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 that Gli1 and Nanog are 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.",

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doi = "10.1074/jbc.M116.714857",

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AU - Li, Qiang

AU - Lex, Rachel K.

AU - Chung, Haewon

AU - Giovanetti, Simone M.

AU - Ji, Zhicheng

AU - Ji, Hongkai

AU - Person, Maria D.

AU - Kim, Jonghwan

AU - Vokes, Steven A.

PY - 2016/3/25

Y1 - 2016/3/25

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AB - 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 toHHsignaling, 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 that Gli1 and Nanog are 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.

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The pluripotency factor NANOG binds to GLI proteins and represses hedgehog-mediated transcription

Abstract

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