Identification of a Novel Enhancer Sequence in the Distal Promoter of the Rat Fatty Acid Synthase Gene

Biochem Biophys Res Commun. 1999 Aug 2;261(2):400-5. doi: 10.1006/bbrc.1999.1034.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Chromosome Mapping
  • DNA / genetics
  • DNA / metabolism
  • Deoxyribonuclease I
  • Enhancer Elements, Genetic*
  • Fasting
  • Fatty Acid Synthases / genetics*
  • Gene Expression Regulation, Enzymologic
  • Liver / enzymology
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Sequence Deletion

Substances

  • RNA, Messenger
  • DNA
  • Fatty Acid Synthases
  • Deoxyribonuclease I