Fig. 7

Schematic model showing cell cycle, p53 signaling, and E2F target gene regulation across HD astrocyte differentiation. a HD NPCs show increased expression of p53 signaling genes, decreased expression of cell cycle and E2F target genes, which coincides with depleted promoter-proximal and distal accessibility of the E2F TF motif, while WT NPCs (b) show normal cell-cycle progression and accessible E2F TF motifs genome-wide. c HD astrocytes show upregulation of p53 signaling, apoptosis, cell cycle and E2F target gene expression, along with increased E2F TF motif accessibility, suggesting cell-cycle re-entry leading to apoptosis. d In comparison, WT astrocytes show depleted accessibility of E2F TF motifs, and have low expression of p53 signaling, E2F target and cell-cycle genes, indicating they are quiescent