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NF‐Y binds to the CCAAT box motif of the FGF‐4 gene and promotes FGF‐4 expression in embryonal carcinoma cells
Author(s) -
Lamb Kimberly A.,
Johnson Lance R.,
Rizzino Angie
Publication year - 1997
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/(sici)1098-2795(199711)48:3<301::aid-mrd1>3.0.co;2-v
Subject(s) - biology , caat box , transcription factor , microbiology and biotechnology , enhancer , fibroblast growth factor , gene expression , embryonic stem cell , ccaat enhancer binding proteins , e box , promoter , reporter gene , regulation of gene expression , electrophoretic mobility shift assay , gene , nuclear protein , genetics , receptor
FGF‐4 appears to be the first fibroblast growth factor (FGF) expressed during embryogenesis, 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. Mol. Reprod. Dev. 48:301–309, 1997. © 1997 Wiley‐Liss, Inc.