UPSTREAM STIMULATORY FACTORS BIND TO INSULIN-RESPONSE SEQUENCE OF THEFATTY-ACID SYNTHASE PROMOTER - USF1 IS REGULATED

Fatty acid synthase (FAS) plays a central role in de novo lipogenesis in mammals, The concentration or activity of FAS in liver and adipose tissue changes dramatically when animals are subjected to nutritional and hormonal manipulations. We previously reported that due to changes in transcription, FAS synthesis declines and increases in an insulin- dependent manner during fasting and refeeding, respectively, and that insulin administration of streptozotocin-diabetic mice stimulates FAS transcription. We previously mapped the FAS insulin response sequence (IRS) to the proximal promoter region from position -71 to position -5 0, which contains an E-box DNA binding motif, Here, using competition gel shift assays and specific upstream stimulatory factor (USF) antibo dies, we identified USF1 and USF2 as major components of complexes tha t bind to the FAS IRS, W-cross-linking experiments further supported t hat USFs bind the FAS IRS, We also found that the amount of the 43-kDa USF1 was dramatically increased in liver of refed rats, In contrast, the amount of USF2 remained the same in liver of fasted or refed rats, Moreover, a 17-kDa protein in both fasted and refed rat liver was rec ognized by anti-USF1 antibodies, and this 17-kDa USF1 related protein was expressed in a manner opposite to that of the 43-kDa USF1, i.e. hi gh in liver of fasted rats and decreased in liver of refed rats. These data suggest that the regulation of USF expression mayplay an importa nt role in the regulation of FAS transcription.