Fig 2: ARID1A loss does not affect the interaction between the SWI/SNF complex and condensin II.(A) Parental control and ARID1A knockout (KO) RMG1 cells were subjected to co-IP analysis using an antibody against a core SWI/SNF subunit BAF155 and examined for interactions with the indicated subunits of the SWI/SNF and condensin I and II complexes by immunoblotting. Asterisks indicate the nonspecific bands in the immunoblotting. (B) Glycerol sedimentation (10 to 30%) assay of the SWI/SNF and condensin II complexes from parental control and ARID1A knockout RMG1 cells. The red box indicates the cosegregation of the SWI/SNF and condensin II complexes. (C) Sucrose sedimentation (10 to 50%) assay of the SWI/SNF and condensin II complexes in ARID1A-mutated TOV21G OCCC cells. The red box indicates the cofractionation of SWI/SNF and condensin II complexes.

Fig 3: Smarcc1 opens Xi promotors in order for the establishment of XCI to proceed.a Xist RNA FISH in female mESCs at differentiation days 4, 5, 6 following knockdown with indicated hairpins. Xist staining green, DAPI blue. b Volume of Xist foci in a. Foci measured (n) are indicated. The line indicates median, box 25th to 75th percentile, error bars 5th to 95th percentile, dots indicate outliers. Two-tailed Student’s unpaired t test, statistically significant p values only given. c–f Smarca4 ChIP-seq in male and female mESCs at differentiation day 4, with Smarcc1 knockdown or non-silencing control, c number macs2 peaks, d coverage plot of X chromosome, e average read density at X-linked genes ±5kb and f an example coverage plot. g Nucleosome occupancy (% GpC methylation) during female mESC differentiation determined by NOMe-seq averaged across genes on the XFVB and XCAST, displayed as a heatmap or smoothed histogram. h Accessibility of XFVB or XCAST promoters during female mESC differentiation determined by NOMe-seq. Line indicates median, box 25th to 75th percentile, error bars 5th to 95th percentile and dots indicate outliers. n = 74 to 261 informative promoters. One-tailed Student’s unpaired t test without outliers, p value is given, non-significance (n.s). i Nucleosome occupancy (% GpC methylation) during female mESC differentiation determined by NOMe-seq averaged across all genes on XFVB upon Smarcc1 knockdown, displayed as a heatmap or smoothed histogram. j Accessibility of XFVB promoters upon Smarcc1 knockdown during female mESC differentiation determined by NOMe-seq. Line indicates the median, box 25th to 75th percentile, error bars 5th to 95th percentile and dots indicate outliers. n = 58 to 261 informative promoters. One-tailed Student’s unpaired t test without outliers, p value is given, non-significance (n.s). k Model for BAF regulation of establishment of XCI. Open and closed chromatin depicted by nucleosome spacing, green lines represent Xist, black arrows transcription and red paddles marked ‘Me’ H3K27me3. This figure depicts timing during differentiation when key XCI events occur; Xist induction (day 3), BAF occupancy at promoters and promoter opening (day 4), failure of gene silencing (day 5) and failure of Xist cloud formation and H3K27me3 deposition (day 6). Source data are provided as a source data file.

Fig 4: Dramatic loss of mSWI/SNF proteins in LSD1 null mice.a Nestin-Cre directed conditional inactivation of mouse Lsd1 gene causes immediate postnatal death after birth (P0). The genomic DNA from the dissected brains from LSD1flox/+, LSD1flox/flox, and LSD1flox/flox/Nestin-Cre mutant mice immediately after birth were extracted and used for genome-typing. b Brain extracts from LSD1flox/+, LSD1flox/flox, and LSD1flox/flox/Nestin-Cre mice were Western blotted for indicated SWI/SNF proteins. Protein molecular weight markers are in kilodaltons (kDa). c Representative brain cryo-sections of postnatal LSD1flox/flox and LSD1flox/flox/Nestin-Cre mice (P0,10-µm thick coronal) were stained with anti-SMARCC1 antibody, counter-stained with 4',6-diamidino-2-phenylindole (DAPI). Scale bar: 500 µm. d Embryonic fibroblasts from CAGGCre-ERTM/LSD1fl/fl mouse embryos (E13.5) were treated with 4-hydroxytamoxifen (20 µg/ml) for 12 h to delete Lsd1 by inducible Actin-Cre-ER. Dimethyl sulfoxide (DMSO) or proteasome inhibitor MG132 (5 µg/ml) was added for the last 6 h before lysing the cells. e HeLa cells were transfected with 50 nM siRNAs of luciferase (Luc), LSD1, LSD1 + SET7 (L + SET7), or SET7 for 48 h and representative Western blots from three independent experiments are shown with Actin as a loading control. Band intensities were quantified by ImageJ software and normalized to the Luciferase (Luc) siRNA control signal. Significance was indicated as a two-tailed, unpaired, t-test. Values are expressed as the mean ± SEM. ***p < 0.001. f H1299 cells stably expressing Flag-tagged SMARCC1 under the retroviral LTR promoter control were transfected with 50 nM of luciferase and LSD1 siRNAs for 48 h and then treated with either dimethyl sulfoxide (DMSO, 1%) or 5 µg/ml MG132 for last 6 h before lysing the cells for Western blotting. g H1299 cells with or without stably expressing Flag-tagged LSD1 cDNA under the retroviral LTR promoter control were transfected with 50 nM of luciferase and LSD1-3’UTR siRNAs for 48 h and a representative blot set is shown for Western blotting. Source data are provided as a Source Data file. Significance was indicated as a two-tailed, unpaired, t-test. Values are expressed as the mean ± SEM. ***p < 0.001. The experiments for a–d and f were repeated three times with the same results.

Fig 5: scRNA-Seq Data Reveal Myeloid and EryD Differentiation Defects from Baf155-Deficient EMPs(A) t-SNE projection of all cells, showing 10 different clusters.(B) Baf155/Smarcc1 expression in all YSs, showing the absence of Baf155 expression in the CKO EMP cell population.(C) An overlay of scRNA-seq data between WT and Baf155 CKO YSs.(D) Percentage of cells in each cluster from WT versus Baf155 CKO YSs.(E) Heatmap showing differentially expressed genes in each cluster.(F) The EMP signature genes Gata2, Tal1, cKit, Cd34, and Pu.1/Spi1 are similarly expressed in WT and Baf155 CKO EMPs.(G) A cell population with myeloid lineage signature gene expression (Irf8, Maf, Csf1r, Cx3cr1, and Trem2) is absent in Baf155 CKO YSs.(H) A cell population with EryD lineage signature genes expression (Gdf3, Muc13, Ccl17, and Gm15915) is significantly lower in Baf155 CKO YSs.(I) A population with elevated megakaryocyte lineage signature gene expression is increased in Baf155 CKO YS cells.(J) Endothelial lineage signature genes are still expressed in the Baf155-deficient EMP cell population.See also Figure S3.