NF-kappaB mediates FGF signal regulation of msx-1 expression.
The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression.
Bushdid
P B
PB
Department of Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA. buslb9@chmcc.org
Chen
C L
CL
Brantley
D M
DM
Yull
F
F
Raghow
R
R
Kerr
L D
LD
Barnett
J V
JV
D000818:Animals; D001665:Binding Sites; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051957:MSX1 Transcription Factor; D016328:NF-kappa B / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors; D015533:Transcriptional Activation
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D014157:Transcription Factors; D005346:Fibroblast Growth Factors