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. Author manuscript; available in PMC: 2023 Oct 8.
Published in final edited form as: ACS Chem Biol. 2023 Aug 21;18(9):2030–2038. doi: 10.1021/acschembio.3c00257

Figure 1: Strategy for and validation of DNMT3A activating screen.

Figure 1:

a) Cartoon showing the original base editor scanning12 and updated strategy for identifying DNMT3A activating mutations. By lowering the background activity of our reporter, we decreased the probability that activating mutations would be hidden by the limited dynamic range between baseline and maximum DNMT3A activity. dDNMT3A = codon-switched DNMT3A2E756A.

b) Cartoon showing our strategy for base editor scanning and separating cells based on DNMT3A activity.

c) Line plot showing silencing over time for rTetR-DNMT3L (v1), DNMT3AWT or DNMT3AWT/R882H (v2) cells. See Figure S2c. for significance testing.

d) Histogram showing silencing of citrine reporter in cells with DNMT3AWT or DNMT3AWT/R882H after 12 days of dox treatment. See Figure S2d. for significance testing.

e) Line plot showing silencing over time of DNMT3AWT or DNMT3AWT/R882H cells with and without the base editing library. Data are mean ± SD of n = 3 replicates. See Figure S2e. for significance testing.