T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
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 beta-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by beta-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by beta-catenin of several non-TCF/LEF-dependent promoters. For example, TCF-4N synergized with beta-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 beta-catenin synergized with the adipogenic transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) to induce leptin promoter activity. The mechanism by which beta-catenin and TCF-4N coactivated C/EBPalpha appeared to involve p300, based upon synergy between these important transcriptional regulators. Consistent with TCF-4N's redirecting the actions of beta-catenin in cells, ectopic expression of TCF-4N in 3T3-L1 preadipocytes partially relieved the block of adipogenesis caused by beta-catenin. Thus, we propose that TCF-4N inhibits coactivation by beta-catenin of TCF/LEF transcription factors and potentiates the coactivation by beta-catenin of other transcription factors, such as SF-1 and C/EBPalpha.
Kennell
Jennifer A
JA
Program in Cellular and Molecular Biology, Division of Endocrinology and Metabolism, University of Michigan Medical School, 1301 E. Catherine Road, Ann Arbor, MI 48109-0622, USA.
O'Leary
Erin E
EE
Gummow
Brian M
BM
Hammer
Gary D
GD
MacDougald
Ormond A
OA
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051717:Fushi Tarazu Transcription Factors; D017930:Genes, Reporter; D018398:Homeodomain Proteins; D006801:Humans; D015151:Immunoblotting; D020738:Leptin / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D010902:Pituitary Gland / Q000166:cytology; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D012190:Retroviridae / Q000235:genetics; D054339:Steroidogenic Factor 1; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin
D022763:CCAAT-Enhancer-Binding Protein-alpha; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D020738:Leptin; D051821:Lymphoid Enhancer-Binding Factor 1; C515057:NR5A1 protein, human; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; C515058:steroidogenic factor 1, mouse; D004247:DNA; D008156:Luciferases