title: Identification of a novel enhancer sequence in the distal promoter of the rat fatty acid synthase gene.
abstract: The proximal promoter and first intron of the fatty acid synthase (FAS) gene contains response sequences for insulin and glucose, but the 2- to 3-fold increase in FAS promoter activity attributable to these sequences falls short of the 20- to 30-fold induction in hepatic FAS gene transcription observed 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 hepatocytes 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 presence of both insulin and glucocorticoids. Deleting HSS 2 abolished the 15-fold induction in FAS promoter activity, but removing HSS 1 was without effect. Apparently the in vivo regulation of hepatic FAS gene transcription requires response elements located in the region of -7300 to -7000 and -265 to +65.
authors.affiliation: Division of Nutritional Science and the Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rufo
authors.forename: D
authors.initials: D
authors.lastname: Gasperikova
authors.forename: S D
authors.initials: SD
authors.lastname: Clarke
authors.forename: M
authors.initials: M
authors.lastname: Teran-Garcia
authors.forename: M T
authors.initials: MT
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D005215:Fasting; D064429:Fatty Acid Synthases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017384:Sequence Deletion
chemical_list: D012333:RNA, Messenger; D004247:DNA; D064429:Fatty Acid Synthases; D003850:Deoxyribonuclease I