Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3

Genes Dev. 1995 Nov 1;9(21):2635-45. doi: 10.1101/gad.9.21.2635.

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

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carcinoma, Embryonal / genetics
  • Carcinoma, Embryonal / pathology
  • Chloramphenicol O-Acetyltransferase / genetics
  • Cloning, Molecular
  • DNA / metabolism
  • DNA, Complementary
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Embryonic and Fetal Development / genetics
  • Enhancer Elements, Genetic*
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental*
  • HMGB Proteins
  • High Mobility Group Proteins / genetics
  • Homeodomain Proteins
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism
  • POU Domain Factors
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • SOXB1 Transcription Factors
  • Trans-Activators / genetics
  • Transcription Factors / genetics*
  • Transcriptional Activation

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • Fgf4 protein, mouse
  • Fibroblast Growth Factor 4
  • HMGB Proteins
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • POU Domain Factors
  • Pou2af1 protein, mouse
  • Proto-Oncogene Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • transcription factor Brn-2
  • Fibroblast Growth Factors
  • DNA
  • Chloramphenicol O-Acetyltransferase

Associated data

  • GENBANK/U31967