Structure and regulation of the avian gene for fatty acid synthase.

Abstract

Starvation, glucagon and cyclic AMP inhibit, and refeeding starved animals and insulin or IGF-I plus triiodothyronine stimulate accumulation of FAS and its mRNA in liver; transcription is the primary regulated step. In the uropygial gland, differentiation of basal cells into mature sebocytes is accompanied by the accumulation of large amounts of FAS and its mRNA. By analogy with liver, transcription is likely to be the regulated step, but direct experimental evidence for this hypothesis is lacking. FAS mRNA is a unique gene and is probably more than 100 kb in length. The FAS gene of goose and duck is transcribed into two mature mRNAs of about 10,800 and 12,200 nucleotides. The 3'-untranslated regions of the FAS mRNAs contain an unusual polypyrimidine tract which, at the mRNA level at least, appears unrelated to regulation of gene expression. Polypyrimidine tracts similar in sequence to that in the FAS gene are found in about 20 different parts of the genome. All of the fragments which contain these tracts are hypermethylated. The next stage of this investigation will involve identification of cis-acting sequence elements in the FAS gene which specify responses to diet, hormones and tissue-specific regulatory factors. Isolation and characterization of the 5'-ends of the cDNA and the gene are underway.