The FIRE3-mediated sterol response of the FAS promoter requires NF-Y/CBF as a coactivator.
The transcription of the fatty acid synthase (FAS) gene is regulated by the sterol status of the cell via cleavage of the sterol regulatory element-binding protein (SREBP). When human HepG2 hepatoma cells were cotransfected with an expression plasmid for mature SREBP-1a together with FAS promoter/reporter constructs significant increases in reporter activity were observed. Deletion analysis of the FAS promoter between -151 and -52 relative to the transcription start site pinpoint two cis-elements important in sterol regulation of the FAS gene. One element, FIRE3, between -71 and -52 can bind in vitro translated and transcribed SREBP-1a whereas the other element, the inverted CCAAT element ICE(-97/-92), binds the trimeric transcription factor NF-Y/CBF as shown with rat liver extract and reconstituted, recombinant NF-Y. The results clearly show that the coactivator for SREBP-1a in this cell line is NF-Y. This finding was confirmed by using a dominant negative form of NF-YA, NF-YAm29, which interferes with the effect of ectopically expressed SREBP-1a on FAS reporter activity.
Wolf
S S
SS
Jenapharm GmbH, Jena, Germany.
Roder
K
K
Sickinger
S
S
Schweizer
M
M
D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics*
D023081:CCAAT-Binding Factor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D019014:fas Receptor; D064429:Fatty Acid Synthases