Cell-type-dependent activity of the ubiquitous transcription factor USF incellular proliferation and transcriptional activation

USF1 and USF2 are basic helix-loop-helix transcription factors implicated i n the control of cellular proliferation, In HeLa cells, the USF proteins ar e transcriptionally active and their overexpression causes marked growth in hibition. In contrast, USF overexpression had essentially no effect on the proliferation of the Saos-2 osteosarcoma cell line. USF1 and USF2 also lack ed transcriptional activity in Saos-2 cells when assayed by transient cotra nsfection with USF-dependent reporter genes. Yet, there was no difference i n the expression, subcellular localization, or DNA-binding activity of the USF proteins in HeLa and Saos-2 cells. Furthermore, Gal4-USF1 and Gal4-USF2 fusion proteins activated transcription similarly in both cell lines. Muta tional analysis and domain swapping experiments revealed that the small, hi ghly conserved USF-specific region (USR) was responsible for the inactivity of USF in Saos-2 cells. In HeLa, the USR serves a dual function. It acts a s an autonomous transcriptional activation domain at promoters containing a n initiator element and also induces a conformational change that is requir ed for USF activity at promoters lacking an initiator. Taken together, thes e results suggest a model in which the transcriptional activity of the USF proteins, and consequently their antiproliferative activity, is tightly con trolled by interaction with a specialized coactivator that recognizes the c onserved USR domain and, in contrast to USF, is not ubiquitous. The activit y of USF is therefore context dependent, and evidence for USF DNA-binding a ctivity in particular cells is insufficient to indicate USF function in tra nscriptional activation and growth control.