QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Cole, M. F. Articles by Young, R. A. PubMed PubMed Citation Articles by Cole, M. F. Articles by Young, R. A. Social Bookmarking                   What's this?

Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells

¹ Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA; ² Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Embryonic stem (ES) cells have a unique regulatory circuitry, largely controlled by the transcription factors Oct4, Sox2, and Nanog, which generates a gene expression program necessary for pluripotency and self-renewal. How external signals connect to this regulatory circuitry to influence ES cell fate is not known. We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus, Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog, and other pluripotency factors and produce ES cells that are refractory to differentiation. Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.

[Keywords: Wnt pathway; embryonic stem cells; Tcf3; regulatory circuitry]]

Received December 12, 2007; revised version accepted January 18, 2008.

⁴ Corresponding author.

E-MAIL young{at}wi.mit.edu; FAX (617) 258-9872.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1642408.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Yi, L. Pereira, and B. J. Merrill Tcf3 Functions as a Steady-State Limiter of Transcriptional Programs of Mouse Embryonic Stem Cell Self-Renewal Stem Cells, August 1, 2008; 26(8): 1951 - 1960. [Abstract] [Full Text] [PDF]