Interaction between a novel F9-specific factor and octamer-binding proteins is required for cell-type-restricted activity of the fibroblast growth factor 4 enhancer.
Understanding how diverse transcription patterns are achieved through common factor binding elements is a fundamental question that underlies much of developmental and cellular biology. One example is provided by the fibroblast growth factor 4 (FGF-4) gene, whose expression is restricted to specific embryonic tissues during development and to undifferentiated embryonal carcinoma cells in tissue culture. Analysis of the cis- and trans-acting elements required for the activity of the previously identified FGF-4 enhancer in F9 embryonal carcinoma cells showed that enhancer function depends on sequences that bind Sp1 and ubiquitous as well as F9-specific octamer-binding proteins. However, sequences immediately upstream of the octamer motif, which conform to a binding site for the high-mobility group (HMG) domain factor family, were also critical to enhancer function. We have identified a novel F9-specific factor, Fx, which specifically recognizes this motif. Fx formed complexes with either Oct-1 or Oct-3 in a template-dependent manner. The ability of different enhancer variants to form the Oct-Fx complexes correlated with enhancer activity, indicating that these complexes play an essential role in transcriptional activation of the FGF-4 gene. Thus, while FGF-4 enhancer function is octamer site dependent, its developmentally restricted activity is determined by the interaction of octamer-binding proteins with the tissue-specific factor Fx.
Rockefeller University, New York, New York 10021.
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Yuan
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Basilico
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051863:Host Cell Factor C1; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3; C494166:Pou2f1 protein, mouse; C494174:Pou5f1 protein, mouse; D011518:Proto-Oncogene Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D005346:Fibroblast Growth Factors