Identification of a novel enhancer sequence in the distal promoter of the rat fatty acid synthase gene

The proximal promoter and first intron of the fatty acid synthase (FAS) gen e contains response sequences for insulin and glucose, but the 2- to 3-fold increase in FAS promoter activity attributable to these sequences falls sh ort of the 20- to 30-fold induction in hepatic FAS gene transcription obser ved in fasted-refed rats. Using DNase I hypersensitivity site (HSS) mapping , two new liver specific sites were localized to the regions of: -8600 to - 8500 (HSS 1) and -7300 to -7000 (HSS 2), DNase sensitivity of the -7300 to -7000 region was increased when fasted rats were refed glucose. When rat he patocytes were transfected with a CAT construct that linked the region of - 9700 and -4606 with the insulin response region located between -265 to +65 , FAS promoter activity was induced 15-fold. This increase required the pre sence of both insulin and glucocorticoids, Deleting HSS 2 abolished the 15- fold induction in FAS promoter activity, but removing HSS 1 was without eff ect. Apparently the in vitro regulation of hepatic FAS gene transcription r equires response elements located in the region of -7300 to -7000 and -265 to +65, (C) 1999 Academic Press.