DIFFERENTIAL ROLES OF UPSTREAM STIMULATORY FACTOR-1 AND FACTOR-2 IN THE TRANSCRIPTIONAL RESPONSE OF LIVER GENES TO GLUCOSE

USF1 and USF2 are ubiquitous transcription factors of the basic helix- loop-helix leucine zipper family. They form homo- and heterodimers and recognize a CACGTG motif termed E box. In the liver, USF binding acti vity is mainly accounted for by the USF1/USF2 heterodimer, which binds irt vitro the glucose/carbohydrate response elements (GlRE/ChoRE) of glucose-responsive genes. To assign a physiological role of USFs in vi vo, we have undertaken the disruption of USF1 and USF2 genes in mice. We present here the generation of USF1-deficient mice. In the liver of these mice, we demonstrate that USFS remaining dimers can compensate for glucose responsiveness, even though the level of total USF binding activity is reduced by half as compared with wild type mice. The resi dual USF1 binding activity was similarly reduced in the previously rep orted USF2 -/- mice in which an impaired glucose responsiveness was ob served (Vallet, V, S,, Henrion, A, A., Bucchini, D., Casado, M., Raymo ndjean, M., Kahn, A., and Vaulont, S. (1997) J. Biol. Chem. 272, 21944 -21949). Taken together, these results clearly suggest differential tr ansactivating efficiencies of USF1 and USF2 in promoting the glucose r esponse. Furthermore, they support the view that USF2 is the functiona l transactivator of the glucose-responsive complex.