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Molecular and Cellular Biology, March 2001, p. 1866-1873, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1866-1873.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Inhibition of Tcf3 Binding by I-mfa Domain Proteins

Lauren Snider,1 Hilary Thirlwell,1 Jeffrey R. Miller,2,dagger Randall T. Moon,2 Mark Groudine,1,3 and Stephen J. Tapscott1,3,*

Fred Hutchinson Cancer Research Center1 and Departments of Neurology and Radiation Oncology, University of Washington Medical Center,3 Seattle, Washington 98109, and Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 981952

Received 20 June 2000/Returned for modification 22 August 2000/Accepted 7 December 2000

We have determined that I-mfa, an inhibitor of several basic helix-loop-helix (bHLH) proteins, and XIC, a Xenopus ortholog of human I-mf domain-containing protein that shares a highly conserved cysteine-rich C-terminal domain with I-mfa, inhibit the activity and DNA binding of the HMG box transcription factor XTcf3. Ectopic expression of I-mfa or XIC in early Xenopus embryos inhibited dorsal axis specification, the expression of the Tcf3/beta -catenin-regulated genes siamois and Xnr3, and the ability of beta -catenin to activate reporter constructs driven by Lef/Tcf binding sites. I-mfa domain proteins can regulate both the Wnt signaling pathway and a subset of bHLH proteins, possibly coordinating the activities of these two critical developmental pathways.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C3-168, P.O. Box 19024, Seattle, WA 98109-1024. Phone: (206) 667-4499. Fax: (206) 667-6524. E-mail: stapscot{at}fred.fhcrc.org.

dagger Present address: Department of Genetics, Cell Biology and Development, University of Minnesota School of Medicine, Minneapolis, MN 55455.

Molecular and Cellular Biology, March 2001, p. 1866-1873, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1866-1873.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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