Transcription factors acting on the promoter of the rat fatty acid synthase gene.
Fatty acid synthase (FAS), one of the main lipogenic enzymes, converts dietary calories into a storage form of energy. The transcription factors, stimulatory proteins 1 and 3 (Sp1 and Sp3), nuclear factor Y (NF-Y), upstream stimulatory factor (USF) and sterol regulatory element binding protein-1 (SREBP-1) have cognate binding sites on the promoter of the FAS gene. It was shown that Sp1 and NF-Y interact co-operatively at the diet-induced DNase I-hypersensitive site at position -500. Adjacent binding sites for NF-Y and Sp1 have also been found between -71 and -52, and -91 and -83. cAMP regulation is mediated via the inverted CAAT element (ICE) at -99 to -92, which binds NF-Y. The FAS insulin-responsive element 3 (FIRE3)-binding site at -71 to -52 is capable of binding NF-Y, USF and SREBP-1, and is required for the sterol response in conjunction with the co-activator NF-Y around -100. Surprisingly, both FIRE3 and ICE are also necessary for the response to retinoic acid that plays a role in development and is an essential component of the diet.
Schweizer
M
M
School of Life Sciences, Heriot-Watt University, Edinburgh, UK. M.Schweizer@hw.ac.uk
Roder
K
K
Zhang
L
L
Wolf
S S
SS
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics*; D050356:Lipid Metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D014157:Transcription Factors; D014212:Tretinoin; D002784:Cholesterol; D064429:Fatty Acid Synthases