Abstract
Fibroblast growth factor 4 (FGF-4) has been shown to be a signaling molecule whose expression is essential for postimplantation mouse development and, at later embryonic stages, for limb patterning and growth. The FGF-4 gene is expressed in the blastocyst inner cell mass and later in distinct embryonic tissues but is transcriptionally silent in the adult. In tissue culture FGF-4 expression is restricted to undifferentiated embryonic stem (ES) cells and embryonal carcinoma (EC) cell lines. Previously, we determined that EC cell-specific transcriptional activation of the FGF-4 gene depends on a synergistic interaction between octamer-binding proteins and an EC-specific factor, Fx, that bind adjacent sites on the FGF-4 enhancer. Through the cloning and characterization of an F9 cell cDNA we now show that the latter activity is Sox2, a member of the Sry-related Sox factors family. Sox2 can form a ternary complex with either the ubiquitous Oct-1 or the embryonic-specific Oct-3 protein on FGF-4 enhancer DNA sequences. However, only the Sox2/Oct-3 complex is able to promote transcriptional activation. These findings identify FGF-4 as the first known embryonic target gene for Oct-3 and for any of the Sox factors, and offer insights into the mechanisms of selective gene activation by Sox and octamer-binding proteins during embryogenesis.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Carcinoma, Embryonal / genetics
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Carcinoma, Embryonal / pathology
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Chloramphenicol O-Acetyltransferase / genetics
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Cloning, Molecular
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DNA / metabolism
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DNA, Complementary
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Embryonic and Fetal Development / genetics
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Enhancer Elements, Genetic*
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Fibroblast Growth Factor 4
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Fibroblast Growth Factors / genetics*
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Fibroblast Growth Factors / metabolism
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Gene Expression Regulation, Developmental*
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HMGB Proteins
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High Mobility Group Proteins / genetics
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Homeodomain Proteins
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Mice
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Molecular Sequence Data
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Nuclear Proteins / genetics*
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism
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POU Domain Factors
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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SOXB1 Transcription Factors
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Trans-Activators / genetics
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Transcription Factors / genetics*
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Transcriptional Activation
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Fgf4 protein, mouse
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Fibroblast Growth Factor 4
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HMGB Proteins
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High Mobility Group Proteins
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Homeodomain Proteins
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Nuclear Proteins
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POU Domain Factors
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Pou2af1 protein, mouse
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Proto-Oncogene Proteins
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Trans-Activators
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Transcription Factors
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transcription factor Brn-2
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Fibroblast Growth Factors
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DNA
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Chloramphenicol O-Acetyltransferase