Figure 3

Indian hedgehog (Ihh) gene expression is markedly reduced in RB^−/− murine osteoblasts. In addition, expression of osteocalcin, another gene for which Runx2 serves as a transcription factor, is reduced in these cells. Chromatin immunoprecipitation analysis reveals that both Runx2 and pRb bind to the Ihh promoter in RB^+/+ cells, while pRb is absent and Runx2 binding is significantly reduced in RB^−/− cells, despite equivalent Runx2 expression. This model posits a chromatin-modifying factor ‘X’ that is recruited to the Runx2 complex by pRb to positively activate Ihh transcription, and a factor ‘Y’ that may alternatively repress Ihh transcription when pRb is not present.