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Molecular and Cellular Biology, August 2003, p. 5366-5375, Vol. 23, No. 15
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.15.5366-5375.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
T-Cell Factor 4N (TCF-4N), a Novel Isoform of Mouse TCF-4, Synergizes with ß-Catenin To Coactivate C/EBP
and Steroidogenic Factor 1 Transcription Factors
Jennifer A. Kennell,1 Erin E. O'Leary,1 Brian M. Gummow,2 Gary D. Hammer,2,3 and Ormond A. MacDougald1,2*
Program in Cellular and Molecular Biology,1
Departments of Molecular and Integrative Physiology,2
Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan Medical School, Ann Arbor, Michigan 48109-06223
Received 26 March 2003/
Returned for modification 5 May 2003/
Accepted 9 May 2003
We have cloned T-cell factor 4N (TCF-4N), an alternative isoform of TCF-4, from developing pituitary and 3T3-L1 preadipocytes. This protein contains the N-terminal interaction domain for ß-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by ß-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by ß-catenin of several non-TCF/LEF-dependent promoters. For example, TCF-4N synergized with ß-catenin to activate the
-inhibin promoter through functional and physical interactions with the orphan nuclear receptor steroidogenic factor 1 (SF-1). In addition, TCF-4N and ß-catenin synergized with the adipogenic transcription factor CCAAT/enhancer binding protein
(C/EBP
) to induce leptin promoter activity. The mechanism by which ß-catenin and TCF-4N coactivated C/EBP
appeared to involve p300, based upon synergy between these important transcriptional regulators. Consistent with TCF-4N's redirecting the actions of ß-catenin in cells, ectopic expression of TCF-4N in 3T3-L1 preadipocytes partially relieved the block of adipogenesis caused by ß-catenin. Thus, we propose that TCF-4N inhibits coactivation by ß-catenin of TCF/LEF transcription factors and potentiates the coactivation by ß-catenin of other transcription factors, such as SF-1 and C/EBP
.
* Corresponding author. Mailing address: Department of Physiology, University of Michigan Medical School, 1301 E. Catherine Rd., Ann Arbor, MI 48109-0622. Phone: (734) 647-4880. Fax: (734) 936-8813. E-mail:
macdouga{at}umich.edu.
Molecular and Cellular Biology, August 2003, p. 5366-5375, Vol. 23, No. 15
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.15.5366-5375.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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