The Transcription Factor Zfp281 Controls Embryonic Stem Cell Pluripotency by Direct Activation and Repression of Target Genes
Article first published online: 28 AUG 2008
Copyright © 2008 AlphaMed Press
Volume 26, Issue 11, pages 2791–2799, November 2008
How to Cite
Wang, Z.-X., Teh, C. H.-L., Chan, C. M.-Y., Chu, C., Rossbach, M., Kunarso, G., Allapitchay, T. B., Wong, K. Y. and Stanton, L. W. (2008), The Transcription Factor Zfp281 Controls Embryonic Stem Cell Pluripotency by Direct Activation and Repression of Target Genes. STEM CELLS, 26: 2791–2799. doi: 10.1634/stemcells.2008-0443
- Issue published online: 9 JAN 2009
- Article first published online: 28 AUG 2008
- Manuscript Accepted: 13 AUG 2008
- Manuscript Received: 13 MAY 2008
- Stem cells;
- Transcription factor;
- Gene regulation
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.