Fig. 6: Competition and cooperation of multiple genes shape base editing outcomes. | Nature Communications

Fig. 6: Competition and cooperation of multiple genes shape base editing outcomes.

From: Elucidating the genetic mechanisms governing cytosine base editing outcomes through CRISPRi screens

Fig. 6

Effects of indicated gene knockdown on editing outcomes at the HEK3 (a) and RNF2 (b) sites in K562 cells. Protospacer sequences are shown at the top, and base editors used are labeled on the left. The top eight, five, and three editing outcomes for rA1-SaBE4(ΔUGI), rA1-SaBE4, and rA1-SaBE1 [rA1-dSaCas9(ΔUGI)] are listed, respectively. Tract plots display absolute frequencies of editing outcomes upon specific gene knockdown (color-coded by gene as indicated). Three negative control samples without knockdown are shown in gray colors, with shaded areas representing ±2 STDs of mean. Dots show individual replicates, and tract lines show averages of n = 2 (b: NCs, UNG, MSH2, LIG3, RFWD3, ERCC4) and n = 3 (all the rest) biological replicates. Horizontal lines show ranges of the replicates for corresponding outcomes. Heatmap shows log2 (fold change) (LFC) in frequencies of editing outcomes relative to the corresponding means of negative controls. *: 1.5 <adjusted z-score <2. **: 2<adjusted z-score <3. ***: adjusted z-score > 3. (c) Proposed mechanisms of cytosine base editing. Competition and cooperation among indicated genes influence base editing outcomes. Dash lines indicate the effects of those genes were only observed in the integrated rA1-SaBE4(ΔUGI) system where only one target C was edited. Created in BioRender. Gu, S. (2025) https://BioRender.com/untq2zw. Source data are provided as a Source Data file.

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