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J Biol Chem. 2016 Mar 25;291(13):7171-82. doi: 10.1074/jbc.M116.714857. Epub 2016 Jan 21.

The Pluripotency Factor NANOG Binds to GLI Proteins and Represses Hedgehog-mediated Transcription.

Author information

1
From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and.
2
Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
3
Institute for Cellular and Molecular Biology, and Proteomics Facility, The University of Texas, Austin, Texas 78712 and.
4
From the Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, and svokes@austin.utexas.edu.

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.

KEYWORDS:

GLI proteins; Hedgehog signaling pathway; Nanog; differentiation; embryonic stem cell; repressor; stem cells; transcription repressor

PMID:
26797124
PMCID:
PMC4807297
DOI:
10.1074/jbc.M116.714857
[Indexed for MEDLINE]
Free PMC Article

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