Activation of FUSE, the far-upstream element, is required for the proper expression of the mammalian gene c-Myc in undifferentiated cells. The binding of FBP (FUSE-binding protein) to FUSE is necessary for c-Myc expression, indicating that FBP functions as a growth-dependent regulator of c-Myc expression. Isolated from proliferating HL60 cells, FBP, FBP2, and FBP3 comprise a family of single-stranded DNA-binding proteins that specifically bind to FUSE elements. The FBP transcription factors share a conserved central DNA-binding domain and show significant homology in their carboxylterminal activation domains. Expression of FBP is detected in undifferentiated cells and is substantially decreased following cellular differentiation.