Fig. 4: Removal of the lamins and LBR displaces and derepresses LADs and other genes.

a,b, The number of genes significantly upregulated (a) and downregulated (b) at least twofold in LBR KO, TKO and QKO mES cells (n = 4 replicates per condition). c, The identification of top unique GO terms in genes differentially expressed between QKO and WT mES cells (GO terms identified by GSEA and reduced by ReVIGO). See also Supplementary Table 3 for the full list of GO terms. d, Analysis of gene expression changes within WT LADs: a comparison of fold change (FC) in gene expression with FC in lamina association (LAP2β) in QKO versus WT mES cells. Of this subset of genes, 489 are significantly upregulated >2-fold (P_adj < 0.05), 286 are significantly downregulated >2-fold (P_adj < 0.05) and 8,266 exhibit no significant change in expression. e,f, LAP2β and H3K9me2 levels (spike-in controlled RPKM) and RNA expression levels for representative upregulated WT LAD gene Serpina3m (e) and downregulated WT LAD gene Slamf6 (f) in WT and QKO mES cells. g,h, H3K9me2 levels (average spike-in controlled RPKM from three replicates) (g) and LAP2β levels (average spike-in controlled RPKM from three replicates) (h) on 489 WT LAD genes upregulated >2-fold in QKO mES cells (d, blue points) and 286 WT LAD genes downregulated >2-fold in QKO mES cells (d, red points), compared with a random sample of 489 non-LAD genes in WT and QKO mES cells. ****P < 0.0001 by Kruskal–Wallis multiple comparisons test with Dunn’s correction. n.s. indicates P > 0.9999. i, Distribution of QKO DEGs across WT domain categories (non-LADs, lamin B1 and LAP2β-associated genes, KODs and LADs). *P < 0.0001 for non-LADs up in QKO versus WT, non-LADs down in QKO versus WT, LB1⁺LAP2β⁺ genes up in QKO, LB1⁺LAP2b⁺ genes down in QKO, LADs up in QKO and LADs down in QKO. *KODs up in QKO (P = 0.0051) and KODs down in QKO (P = 0.0415). Analysis of significant enrichment of DEGs in a domain class by two-sided Fisher’s exact test.

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