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EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS

The Transcription Factor Zfp281 Controls Embryonic Stem Cell Pluripotency by Direct Activation and Repression of Target Genes

^aDepartment of Hepatobilliary Surgery, Lanzhou Jin Cheng Hospital, Lan Zhou, People's Republic of China;
^bStem Cell and Developmental Biology, Genome Institute of Singapore, Singapore;
^cDepartment of Biological Sciences, National University of Singapore

Key Words. Stem cells • Pluripotency • Transcription factor • Differentiation • Gene regulation

Correspondence: Correspondence: Lawrence W. Stanton, Ph.D., Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672. Telephone: 65-6478-8000; Fax: 65-6478-9051; e-mail: stantonl{at}gis.a-star.edu.sg

Received on May 13, 2008; accepted for publication on August 13, 2008.

First published online in STEM CELLS EXPRESS  August 28, 2008.

Oct4, Sox2, and Nanog are key components of a core transcriptional regulatory network that controls the ability of embryonic stem cells to differentiate into all cell types. Here we show that Zfp281, a zinc finger transcription factor, is a key component of the network and that it is required to maintain pluripotency. Zfp281 was shown to directly activate Nanog expression by binding to a site in the promoter in very close proximity to the Oct4 and Sox2 binding sites. We present data showing that Zfp281 physically interacts with Oct4, Sox2, and Nanog. Chromatin immunoprecipitation experiments identified 2,417 genes that are direct targets for regulation by Zfp281, including several transcription factors that are known regulators of pluripotency, such as Oct4, Sox2, and Nanog. Gene expression microarray analysis indicated that some Zfp281 target genes were activated, whereas others were repressed, upon knockdown of Zfp281. The identification of both activation and repression domains within Zfp281 suggests that this transcription factor plays bifunctional roles in regulating gene expression within the network.

Disclosure of potential conflicts of interest is found at the end of this article.