Fibroblast growth factor receptor 3 gene: regulation by serum response factor.
We have previously identified a cis-acting sequence in the proximal promoter of the fibroblast growth factor receptor 3 (FGFR3) gene that strongly activates transcription in chondrocytic cells. Here we report that the transcriptional activity of this sequence (FRE3) requires serum response factor and its cognate recognition motif, serum response element. Although the FRE3 contains consensus sequence motifs for several transcription factors, the serum response element is paramount for the transcriptional activity of the FRE3. Additionally, the transcriptional activity of the proximal promoter of the FGFR3 gene is suppressed by mutation of the serum response element. Serum response factor binds to the FRE3 as evidenced by gel shift experiments and antibody supershift experiments and expression of a dominant negative form of serum response factor suppresses the activity of FRE3. Additionally, serum response factor binds to the FGFR3 gene in vivo, as demonstrated by chromatin immunoprecipitation. Serum response factor is an important regulator of cardiac, skeletal, and smooth muscle gene expression; these data suggest that serum response factor is also an important determinant of chondrocyte gene expression.
Reinhold
Martina I
MI
Department of Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA.
McEwen
Donald G
DG
Naski
Michael C
MC
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019902:Chondrocytes / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D026362:Serum Response Factor / Q000502:physiology*; D013698:Templates, Genetic; D014158:Transcription, Genetic / Q000235:genetics
D017468:Receptors, Fibroblast Growth Factor; D026362:Serum Response Factor; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3