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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{alpha} 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 {alpha}-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 {alpha} (C/EBP{alpha}) to induce leptin promoter activity. The mechanism by which ß-catenin and TCF-4N coactivated C/EBP{alpha} 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{alpha}.


* 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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