(A) Schematic representation of the engineered p21 gene locus
containing MS2 stem-loops (p21-MS2). The transcription start site is shown as an arrow, exons
are shown as blue rectangles, introns are shown as angled lines, and 5’ and 3’
untranslated regions (UTRs) are in gray. Scale bar, 1 kb. (B) Live-cell imaging of
U2OS p21-MS2 cells in untreated medium. Top panel: Images of cells containing p21-MS2 (maximum
intensity projections of z-dimension stacks). Scale bar, 10 μm; the green box outlines
the transcription site (TS). Bottom panel: Quantification of the fluorescence intensity at the
TS marked in the top panel. (C) Live-cell imaging of U2OS p21-MS2 cells in
ALRN-6924-treated medium as described in (B). (D) Proportion of cells containing
an active TS (>1.5-fold the background). For each time point and condition, the
proportion of active TS in a cell population was calculated using a rolling average of 30 min
before and after each time point [85 untreated cells (top) and 54 cells treated with 5
μM ALRN-6924 (bottom)]. The pink area represents the 95% confidence interval.
(E) Average cumulative transcription plot of p21-MS2 gene in untreated (green
broken lines) versus ALRN-6924-treated cells (red solid lines). MCP-GFP, green fluorescent
protein-tagged MS2 capsid protein; a.u., arbitrary units.