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PMID: 7969117 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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.

Molecular and cellular biology ·Vol. 14 ·No. 12 ·1994-12-00 ·Pages 7758-69

Dailey L, Yuan H, Basilico C

Abstract

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.

MeSH Terms
Animals Base Sequence Cell Line DNA-Binding Proteins/metabolism Enhancer Elements, Genetic Fibroblast Growth Factor 4 Fibroblast Growth Factors/genetics Gene Expression Regulation, Developmental Host Cell Factor C1 Macromolecular Substances Mice Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/metabolism Octamer Transcription Factor-1 Octamer Transcription Factor-3 Proto-Oncogene Proteins/genetics Sp1 Transcription Factor/metabolism Structure-Activity Relationship Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins Fgf4 protein, mouse Fibroblast Growth Factor 4 Hcfc1 protein, mouse Host Cell Factor C1 Macromolecular Substances Nuclear Proteins Octamer Transcription Factor-1 Octamer Transcription Factor-3 Pou2f1 protein, mouse Pou5f1 protein, mouse Proto-Oncogene Proteins Sp1 Transcription Factor Transcription Factors Fibroblast Growth Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dailey L
Rockefeller University, New York, New York 10021.
Yuan H
Basilico C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.12.7758-7769.1994
Published
1994-12-00
Pages
7758-69
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359316
Subset
IM
Grants
NCI NIH HHS · CA45689 · United States
NCI NIH HHS · CA49472 · United States
External Links
PubMed source DOI: 10.1128/mcb.14.12.7758-7769.1994 PMC Full Text View journal details
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