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EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS |
aDepartment of Biological Sciences, National University of Singapore, Singapore;
bGene Regulation Laboratory, Genome Institute of Singapore, Singapore
Key Words. Zfp143 • Oct4 • Nanog • Embryonic stem cell
Correspondence: Correspondence: Huck-Hui Ng, Ph.D., Genome Institute of Singapore, 60 Biopolis Street, #02-01, Genome Building, Singapore 138672. Telephone: 65-6478-8145; Fax: 65-6478-9004; e-mail: nghh{at}gis.a-star.edu.sg
Received on April 22, 2008;
accepted for publication on July 22, 2008.
First published online in STEM CELLS EXPRESS August 7, 2008.
Identification of regulators governing the maintenance of embryonic stem (ES) cells is crucial to the understanding of ES cell biology. We identified a zinc finger protein, Zfp143, as a novel regulator for self-renewal. Depletion of Zfp143 by RNA interference causes loss of self-renewal of ES cells. Chromatin immunoprecipitation and electrophoretic mobility shift assays show the direct binding of Zfp143 to the Nanog proximal promoter. Knockdown of Zfp143 or mutation of the Zfp143 binding motif significantly downregulates Nanog proximal promoter activity. Importantly, enforced expression of Nanog is able to rescue the Zfp143 knockdown phenotype, indicating that Nanog is one of the key downstream effectors of Zfp143. More interestingly, we further show that Zfp143 regulates Nanog expression through modulation of Oct4 binding. Coimmunoprecipitation experiments revealed that Zfp143 and Oct4 physically interact with each other. This interaction is important because Oct4 binding to the Nanog promoter is promoted by Zfp143. Our study reveals a novel regulator functionally important for the self-renewal of ES cells and provides new insights into the expanded regulatory circuitry that maintains ES cell pluripotency.
Disclosure of potential conflicts of interest is found at the end of this article.
This article has been cited by other articles:
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