Zfp143 regulates Nanog through modulation of Oct4 binding

¹ Dept of Biological Sciences, National University of Singapore, Singapore 117543.; Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672.
² Dept of Biological Sciences, National University of Singapore, Singapore 117543.

^* To whom correspondence should be addressed. E-mail: nghh{at}gis.a-star.edu.sg.

	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 selfrenewal. Depletion of Zfp143 by RNAi causes loss of self-renewal of ES cells. Chromatin immunoprecipitation and EMSA show the direct binding of Zfp143 to Nanog proximal promoter. Knockdown of Zfp143 or mutation of Zfp143 binding motif significantly down-regulates 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 Nanog promoter is promoted by Zfp143. Our study reveals a novel regulator functionally important for the selfrenewal of ES cells and provides new insights into the expanded regulatory circuitry that maintains ES cell pluripotency.