The fatty acid synthase (FAS) gene and its promoter in Rattus norvegicus

Abstract

Screening of rat liver genomic libraries yielded 5 overlapping clones for rat fatty acid synthase (FAS). From these clones we determined the 18,170 bp sequence of the rat FAS together with 5,028 bp of the 5′-flanking region and 515 bp of the 3′-adjacent genomic sequence. The two FAS transcripts which differ only in the positions of their poly-adenylation/termination sites consist of one untranslated and 42 translated exons. Surprisingly, the substrate binding site for enoyl reductase, one of the FAS component functions, is interrupted by an intron. The sizes and the boundaries of the individual domains could be mapped in relation to the exon/intron structure of the gene. These eight partial functions coincide with discrete units of exons. The acyl carrier protein with its prosthetic 4′-phosphopantetheine group is located within a single exon supporting the idea that rat FAS has evolved by gene fusion.

Using primer extension the main transcription start site of the FAS mRNA in both hepatic and mammary gland tissues was located at 5,028 bp in the sequence determined. As expected of a gene which is pretranslationally regulated the 5′-flanking region contains, in addition to TATA and CAAT boxes, consensus sequences for several DNA binding proteins.

Key Words:

• extended fatty acid synthase (FAS) cDNA
• mosaic structure
• promoter
• sizes of the eight domains
• substrate binding sites
• transcriptional regulatory elements