Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3.
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.
Yuan
H
H
Department of Microbiology, New York University School of Medicine, New York 10016, USA.
Corbi
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N
Basilico
C
C
Dailey
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000473:pathology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics; D004742:Enhancer Elements, Genetic; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D050809:POU Domain Factors; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D024002:HMGB Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D050809:POU Domain Factors; C490424:Pou2af1 protein, mouse; D011518:Proto-Oncogene Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C085076:transcription factor Brn-2; D005346:Fibroblast Growth Factors; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase