Nucleic Acids Research Advance Access originally published online on September 13, 2006
Nucleic Acids Research 2006 34(17):4780-4790; doi:10.1093/nar/gkl631
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Nucleic Acids Research, 2006, Vol. 34, No. 17 4780-4790
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Zfp206 regulates ES cell gene expression and differentiation
1 Department of Molecular and Medical Genetics, University of Toronto #4388 Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8 Canada 2 Institute for Biomaterials and Biomedical Engineering 164 College Street Room 407, Toronto, ON M5S 3G9 Canada 3 The Hospital for Sick Children 101 College Street Room 13-305, Toronto, ON M5G 1L7 Canada 4 Banting and Best Department of Medical Research, University of Toronto 112 College Street, Toronto, ON M5G 1L6 Canada
*To whom correspondence should be addressed. Tel: 416 946 8260; Fax: 416 978 8528; Email: t.hughes{at}utoronto.ca
Received July 25, 2006. Revised August 8, 2006. Accepted August 9, 2006.
Understanding transcriptional regulation in early developmental stages is fundamental to understanding mammalian development and embryonic stem (ES) cell properties. Expression surveys suggest that the putative SCAN-Zinc finger transcription factor Zfp206 is expressed specifically in ES cells [Zhang,W., Morris,Q.D., Chang,R., Shai,O., Bakowski,M.A., Mitsakakis,N., Mohammad,N., Robinson,M.D., Zirngibl,R., Somogyi,E. et al., (2004) J. Biol., 3, 21; Brandenberger,R., Wei,H., Zhang,S., Lei,S., Murage,J., Fisk,G.J., Li,Y., Xu,C., Fang,R., Guegler,K. et al., (2004) Nat. Biotechnol., 22, 707–716]. Here, we confirm this observation, and we show that ZFP206 expression decreases rapidly upon differentiation of cultured mouse ES cells, and during development of mouse embryos. We find that there are at least six isoforms of the ZFP206 transcript, the longest being predominant. Overexpression and depletion experiments show that Zfp206 promotes formation of undifferentiated ES cell clones, and positively regulates abundance of a very small set of transcripts whose expression is also specific to ES cells and the two- to four-cell stages of preimplantation embryos. This set includes members of the Zscan4, Thoc4, Tcstv1 and eIF-1A gene families, none of which have been functionally characterized in vivo but whose members include apparent transcription factors, RNA-binding proteins and translation factors. Together, these data indicate that Zfp206 is a regulator of ES cell differentiation that controls a set of genes expressed very early in development, most of which themselves appear to be regulators.
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