Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 291, Issue 13, Pages 7171-7182Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.714857
Keywords
differentiation; embryonic stem cell; Hedgehog signaling pathway; stem cells; transcription repressor; GLI proteins; Nanog; repressor
Categories
Funding
- National Institutes of Health [R01HG006282, R01HD073151]
- Cancer Prevention Research Institute of Texas [RP120343, RP110782]
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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 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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