Differential roles of upstream stimulatory factors 1 and 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 activity is mainly accounted for by the USF1/USF2 heterodimer, which binds in vitro the glucose/carbohydrate response elements (GlRE/ChoRE) of glucose-responsive genes. To assign a physiological role of USFs in vivo, 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 USF2 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 residual USF1 binding activity was similarly reduced in the previously reported USF2 -/- mice in which an impaired glucose responsiveness was observed (Vallet, V. S., Henrion, A. A., Bucchini, D., Casado, M. , Raymondjean, M., Kahn, A., and Vaulont, S. (1997) J. Biol. Chem. 272, 21944-21949). Taken together, these results clearly suggest differential transactivating efficiencies of USF1 and USF2 in promoting the glucose response. Furthermore, they support the view that USF2 is the functional transactivator of the glucose-responsive complex.
Institut Cochin de Génétique Moléculaire, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
V S
VS
Vallet
M
M
Casado
A A
AA
Henrion
D
D
Bucchini
M
M
Raymondjean
A
A
Kahn
S
S
Vaulont
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis; D019281:Dimerization; D005786:Gene Expression Regulation / Q000235:genetics*; D005947:Glucose / Q000494:pharmacology*; D008099:Liver / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics; D011770:Pyruvate Kinase / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C051065:THRSP protein, human; C501477:Thrsp protein, mouse; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; C497186:Usf2 protein, mouse; D011770:Pyruvate Kinase; D005947:Glucose