Figure 3. Stem/progenitor cells and sensitivity to pRb loss.

The figure summarizes the hypothesis that there exists an inverse correlation between differentiation and sensitivity to pRb loss. Stem/progenitor cells are relatively undifferentiated and have a neutral chromatin state at key lineage specifying regulatory genes. Chromatin at such genes is characterized by the simultaneous presence of protein complexes and chromatin marks characteristic of both open (shapes marked +) and closed chromatin (shapes marked −). pRb is typically associated with factors that create a closed chromatin state repressive for transcription (although there are notable exceptions). Loss of pRb in such cells is expected to have a large effect on gene expression as it will tip the balance in favor gene expression. In more differentiated cells, chromatin is more rigidly committed to an open or closed state by multiple, redundant mechanisms. Loss of pRb in such cells is expected to have less effect on the expression of stably repressed genes as there are redundant mechanisms in place to maintain the closed chromatin state.