Fig. 6: Conserved dosage sensitivity in human lung epithelial cells.

a, Western blot analysis of BRG1 in BRM-knockout (KO) BEAS-2B cells after treatment with the indicated concentrations of AU-15330 for 24 h (top). Data are presented as the mean ± s.e.m. from four independent experiments. Quantification of relative BRG1 abundance following AU-15330 treatment (bottom). BRG1 expression relative to that of tubulin was normalized to DMSO-treated (0 nM) BRM-KO BEAS-2B cells. b, PCA of ATAC-seq data across different AU-15330 concentrations. Cells were treated with AU-15330 for 24 h. c, Pie chart depicting relative percentages of significantly changed ATAC-seq signals at promoters, enhancers and insulators. d, Pie charts depicting percentages of significantly changed ATAC-seq signals at BRG1 target sites in promoters, enhancers and insulators. e, Heatmap showing profiles of protein and histone modifications (CUT&RUN and ChIP–seq⁸⁹) (red) and ATAC-seq (blue) for regions falling into genomic elements at the indicated dTAG13 concentration (bottom). The top panel shows aggregate coverage plots with mean enrichment at promoters (red), enhancers (cyan) and insulators (orange). f, Histogram of delta values for BRG1-dependent regulatory elements (promoters + enhancers + insulators). g, Histograms of delta values for BRG1-dependent promoters, enhancers and insulators. The red line indicates delta = 0. h, Chromatin accessibility changes for each of the five groups of BRG1-dependent enhancers in BEAS-2B cells. Lines show the mean of each group, shaded areas indicate the s.e.m. i, Heatmap showing relative enrichment of chromatin marks and MED1 binding across different groups of ATAC-seq peaks. j, Number of SEs in each group. k, MYC expression relative to that of GAPDH at different BRG1 levels. The level was further normalized by 0 nM AU-15330 conditions. Data represent three independent replicates, each with three technical replicates. Bars indicate the average.

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