Zfp143 Regulates Nanog Through Modulation of Oct4 Binding

Authors

  • Xi Chen,

    1. Department of Biological Sciences, National University of Singapore, Singapore
    2. Gene Regulation Laboratory, Genome Institute of Singapore, Singapore
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  • Fang Fang,

    1. Department of Biological Sciences, National University of Singapore, Singapore
    2. Gene Regulation Laboratory, Genome Institute of Singapore, Singapore
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  • Yih-Cherng Liou,

    1. Department of Biological Sciences, National University of Singapore, Singapore
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  • Huck-Hui Ng

    Corresponding author
    1. Department of Biological Sciences, National University of Singapore, Singapore
    2. Gene Regulation Laboratory, Genome Institute of Singapore, Singapore
    • 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
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Abstract

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.

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