The tripartite DNA element responsible for diet-induced rat fatty acid synthase (FAS) regulation

Abstract We investigated which region of the 5′-flanking sequence of the rat fatty acid synthase (FAS)-encoding gene could be responsible for its nutritionally regulated expression. Diet-induced differences in chromatin structure were determined by DNase I treatment of intact nuclei from hepatic tissue. A low-fat diet results in a different pattern of DNase I-hypersensitive sites ( HS ) in the chromatin of the FAS promoter ( pFAS ) from that seen when the nuclear extract was prepared from the livers of normally fed rats. The protein-binding properties of the region defined by DNase I hypersensitivity were tested by gel retardation. A putative cis -acting element with a tripartite structure, 5′-GCCT, 6-bp spacer and a 3′-palindrome, could be localized between bp − 518 to − 495 in pFAS . Competition experiments with oligodeoxyribo-nucleotides (oligos) representing subfragments of this cis -element showed that the requirement for structure is stricter than that for sequence. This element could be one of the termini of the insulin-induced signal cascade.