FIGURE 10.

Hypothetical regulatory mechanism for the transcriptional regulation of Rb gene by FBI-1 and Sp1. When FBI-1 is highly expressed as in cancer cells, FBI-1 binds to the distal FREs and GC-box 2 on the Rb promoter by competing with Sp1. FBI-1 preferentially binds to FRE2 (⋆⋆). After FBI-1 binding, the co-repressor-HDAC complex is recruited by the POZ-domain of FBI-1 and represses transcription by deacetylating histones H3 and H4 of the nucleosomes around the proximal promoter. When FBI-1 is low, as in normal cells, Sp1 binds to FRE3 (††), a newly identified strong Sp1-binding element, GC-box 1, and GC-box 2 to activate transcription. FRE, FBI-1 binding element; GC-box, Sp1-binding GC-rich element; ⋆⋆, high affinity FBI-1 binding element; ⋆, high affinity FBI-1 binding GC-box2 element; ††, a newly identified high affinity Sp1-binding element; Tsp (+1), transcription start site; ⊥ transcription repression by histone modification at the proximal promoter.