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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 25 OCT 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 11, pages 1705–1716, November 2011
How to Cite
Fidalgo, M., Shekar, P. C., Ang, Y.-S., Fujiwara, Y., Orkin, S. H. and Wang, J. (2011), Zfp281 Functions as a Transcriptional Repressor for Pluripotency of Mouse Embryonic Stem Cells. STEM CELLS, 29: 1705–1716. doi: 10.1002/stem.736
Author contributions: M.F. and P.C.S.: collection and assembly of data, data analysis and interpretation; Y.-S.A.: bioinformatics data analysis; Y.F.: collection of data and manuscript approval; S.H.O.: data interpretation and manuscript approval; J.W.: conception, design, collection and assembly of data, data analysis and interpretation, manuscript writing and final approval of manuscript. M.F. and P.C.S. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS September 13, 2011.
- Issue published online: 25 OCT 2011
- Article first published online: 25 OCT 2011
- Accepted manuscript online: 13 SEP 2011 12:38PM EST
- Manuscript Accepted: 31 AUG 2011
- Manuscript Received: 28 JUN 2011
- Black Family Stem Cell Institute at Mount Sinai School of Medicine
- New York State Stem Cell Science (NYSTEM)
- New York State Department of Health. Grant Number: N09G315
- NIH. Grant Number: 1R01-GM095942-01A1
- Embryonic stem cells;
- Transcriptional repressor;
Embryonic stem cells (ESCs) derived from preimplantation blastocysts have unique self-renewal and multilineage differentiation properties that are controlled by key components of a core regulatory network including Oct4, Sox2, and Nanog. Understanding molecular underpinnings of these properties requires identification and characterization of additional factors that act in conjunction with these key factors in ESCs. We have previously identified Zfp281, a Krüppel-like zinc finger transcription factor, as an interaction partner of Nanog. We now present detailed functional analyses of Zfp281 using a genetically ablated null allele in mouse ESCs. Our data show that while Zfp281 is dispensable for establishment and maintenance of ESCs, it is required for their proper differentiation in vitro. We performed microarray profiling in combination with previously published datasets of Zfp281 global target gene occupancy and found that Zfp281 mainly functions as a repressor to restrict expression of many stem cell pluripotency genes. In particular, we demonstrated that deletion of Zfp281 resulted in upregulation of Nanog at both the transcript and protein levels with concomitant compromised differentiation of ESCs during embryoid body culture. Chromatin immunoprecipitation experiments demonstrated that Zfp281 is required for Nanog binding to its own promoter, suggesting that Nanog-associated repressive complex(es) involving Zfp281 may fine-tune Nanog expression for pluripotency of ESCs. STEM CELLS 2011;29:1705–1716