FIG. 1.

OSI-2040 increases γ-promoter activity and endogenous fetal globin expression. (A) Diagrammatic representation of the HS2-γ–luciferase construct used for screening compounds from fungus libraries. The open box represents the HindIII-BglII fragment of HS2, and the shaded box represents the −260 γ-promoter–luciferase reporter gene. (B) Dose-response curve of γ-promoter induction with OSI-2040. K562 cells containing the HS2-γ–luciferase construct were exposed to increasing concentrations of OSI-2040 as indicated. After 24 h, the cells were lysed and the reporter gene activity was measured and plotted as the induction compared with that of uninduced control K562 cells. The OSI-2040 dose axis is not to scale. (C) Benzidine staining in cells treated with γ-gene inducers. K562 cells were treated with OSI-2040 (0.8 mM), butyrate (1 mM), or hydroxyurea (500 mM) for 96 h. Untreated K562 cells served as a control.