Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
3T3 Cells
-
Adipocytes / metabolism
-
Animals
-
CCAAT-Enhancer-Binding Protein-alpha / metabolism*
-
Cell Differentiation
-
Cell Line
-
Cloning, Molecular
-
Cytoskeletal Proteins / metabolism*
-
DNA / metabolism
-
DNA-Binding Proteins / metabolism*
-
Fushi Tarazu Transcription Factors
-
Genes, Reporter
-
Homeodomain Proteins
-
Humans
-
Immunoblotting
-
Leptin / metabolism
-
Luciferases / metabolism
-
Lymphoid Enhancer-Binding Factor 1
-
Mice
-
Models, Biological
-
Models, Genetic
-
Pituitary Gland / cytology
-
Plasmids / metabolism
-
Precipitin Tests
-
Promoter Regions, Genetic
-
Protein Binding
-
Protein Isoforms
-
Protein Structure, Tertiary
-
Receptors, Cytoplasmic and Nuclear
-
Retroviridae / genetics
-
Steroidogenic Factor 1
-
TCF Transcription Factors
-
Trans-Activators / metabolism*
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors / chemistry*
-
Transcription Factors / metabolism*
-
Transcription Factors / physiology*
-
Transcription, Genetic
-
Transfection
-
beta Catenin
Substances
-
CCAAT-Enhancer-Binding Protein-alpha
-
CTNNB1 protein, human
-
CTNNB1 protein, mouse
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
Fushi Tarazu Transcription Factors
-
Homeodomain Proteins
-
Leptin
-
Lymphoid Enhancer-Binding Factor 1
-
NR5A1 protein, human
-
Protein Isoforms
-
Receptors, Cytoplasmic and Nuclear
-
Steroidogenic Factor 1
-
TCF Transcription Factors
-
TCF7L2 protein, human
-
Tcf7l2 protein, mouse
-
Trans-Activators
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors
-
beta Catenin
-
steroidogenic factor 1, mouse
-
DNA
-
Luciferases