TY - JOUR
T1 - NF-Y binds to the CCAAT box motif of the FGF-4 gene and promotes FGF-4 expression in embryonal carcinoma cells
AU - Lamb, Kimberly A.
AU - Johnson, Lance R.
AU - Rizzino, Angie
PY - 1997/11
Y1 - 1997/11
N2 - FGF-4 appears to be the first fibroblast growth factor (FGF) expressed during embryo-genesis, and its expression is critical for early mammalian development. FGF-4 is expressed in the embryonic cell lines, F9, D3, and NT2/D1; but its expression in these cells is repressed upon differentiation. Transcription of the FGF-4 gene in embryonic cells is regulated by an enhancer in the third exon and by a positive regulatory region upstream of the transcription start site. A CCAAT box motif within the positive regulatory region has been shown to support FGF-4 expression, but the factor that binds to this site in vivo has not been identified. In this report, we demonstrate that the transcription factor complex NF-Y binds to the FGF-4 CCAAT box motif when nuclear extracts from each of the embryonic cell lines and their differentiated cells were examined by gel mobility shift analyses. Importantly, we demonstrate that expression of a dominant-negative NF-YA mutant protein reduces the expression of FGF-4 promoter/reporter gene constructs in F9 EC cells. Hence, we provide strong evidence that the transcription factor NF-Y is involved in the expression of the FGF-4 gene.
AB - FGF-4 appears to be the first fibroblast growth factor (FGF) expressed during embryo-genesis, and its expression is critical for early mammalian development. FGF-4 is expressed in the embryonic cell lines, F9, D3, and NT2/D1; but its expression in these cells is repressed upon differentiation. Transcription of the FGF-4 gene in embryonic cells is regulated by an enhancer in the third exon and by a positive regulatory region upstream of the transcription start site. A CCAAT box motif within the positive regulatory region has been shown to support FGF-4 expression, but the factor that binds to this site in vivo has not been identified. In this report, we demonstrate that the transcription factor complex NF-Y binds to the FGF-4 CCAAT box motif when nuclear extracts from each of the embryonic cell lines and their differentiated cells were examined by gel mobility shift analyses. Importantly, we demonstrate that expression of a dominant-negative NF-YA mutant protein reduces the expression of FGF-4 promoter/reporter gene constructs in F9 EC cells. Hence, we provide strong evidence that the transcription factor NF-Y is involved in the expression of the FGF-4 gene.
KW - Cis-regulatory element
KW - Embryonal carcinoma
KW - Embryonic stem
KW - Fibroblast growth factor
KW - Gel mobility shift analysis
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U2 - 10.1002/(SICI)1098-2795(199711)48:3<301::AID-MRD1>3.0.CO;2-V
DO - 10.1002/(SICI)1098-2795(199711)48:3<301::AID-MRD1>3.0.CO;2-V
M3 - Article
C2 - 9322240
AN - SCOPUS:0030767478
VL - 48
SP - 301
EP - 309
JO - Molecular Reproduction and Development
JF - Molecular Reproduction and Development
SN - 1040-452X
IS - 3
ER -