DNA binding of USF is required for specific E-box dependent gene activation in vivo

Although USF-1 and -2 are the major proteins that bind to Myc-regulated E-b ox (CACGTG) elements in many cells, there is no clear role for USF during M yc-dependent gene regulation. Using dominant negative alleles of USF-1 we n ow show that DNA binding by USF at a MSc-regulated E-box limits the ability of another E-box binding factor, TFE-3, to activate a target gene of Myc i ll vivo and to stimulate S phase entry in resting fibroblasts, Similarly, d ominant negative alleles of USF-1 relieve the restriction that presents act ivation of the IgH enhancer by TFE-3 in non B-cells, DNA binding activity o f USF complexes is abundant in primary human B-cells and is significantly d ownregulated during B-cell immortalization, Re-expression of USF-1 in immor talized B-cells retards proliferation. Our data establish an essential role for USF in restricting E-box dependent gene activation ill vivo and sugges t that this control is relaxed during cellular immortalization.