NF-Y involvement in the polyunsaturated fat inhibition of fatty acid synthase gene transcription.
Dietary polyunsaturated fats (PUFA) reduce the hepatic content of SREBP-1 65-75%, and this is paralleled by a comparable decrease in the expression of fatty acid synthase (FAS) gene. The close association between the nuclear content of SREBP-1 and FAS transcription has led to the conclusion that PUFA inhibit lipogenic gene transcription by suppressing SREBP-1 expression, but this conclusion is based upon correlative data. When in fact the SREBP-1/USF sites of the insulin response element of FAS were mutated, only 25% of the PUFA inhibition of FAS promoter activity was lost. On the other hand, mutating the -99/-93 NF-Y site reduced overall promoter activity 85%, and eliminated 50% of the PUFA suppression of FAS promoter activity. In addition, extended cloning and transfection-reporter assays revealed that the FAS gene contains a second PUFA response region (PUFA-RR) in the distal area of -7382/-6970. Interestingly, the distal PUFA-RR(FAS) has many similarities to the PUFA-RR of l-pyruvate kinase gene while the proximal PUFA-RR(FAS) is comparable to the PUFA-RR of the S14 and stearoyl-CoA desaturase genes.
Teran-Garcia
Margarita
M
Division of Nutritional Sciences, University of Texas, Austin 78712, USA.
Rufo
Caterina
C
Nakamura
Manabu T
MT
Osborne
Timothy F
TF
Clarke
Steven D
SD
D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D051720:Upstream Stimulatory Factors
D023081:CCAAT-Binding Factor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004042:Dietary Fats, Unsaturated; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497182:Usf1 protein, rat; D064429:Fatty Acid Synthases