Fig. 5
From: Sex-biased and parental allele-specific gene regulation by KDM6A
Allelic changes in H3K27me3 and chromatin accessibility after Kdm6a KO in BC and CB clones. A, B Box plots show average ratios of H3K27me3 (A) and ATAC-seq (B) read coverage between clone Kdm6aΔE1 and wt cells at promoters (± 2 kb of the TSS) on maternal alleles. Both downregulated groups (A and B) show a significant increase in H3K27me3 levels on maternal alleles (A **p = 0.001; B ***p = 5.33e−06). Maternally downregulated genes (group A) show significant loss of chromatin accessibility (***p = 5.9e−11) on the maternal allele in KO cells, while paternally downregulated genes (group B) do not. Upregulated groups (D and E) show no or slight changes in H3K27me3 (E *p = 0.020), and show the expected increase in chromatin accessibility (D ***p = 2.4e−07; E *p = 0.03). Values were normalized to the input and converted to log scale. C UCSC Genome browser (GRCm38/mm10) view of maternal H3K27me3 and chromatin accessibility profiles in wt (−) and Kdm6aΔE1 ( +) at the maternally downregulated gene Exoc8 shows an increase in H3K27me3 and a corresponding decrease in ATAC-seq around the promoter. D, E Same analysis as in (A, B) but for paternal alleles. Both downregulated groups (A and B) show an increase in H3K27me3 levels (A ***p = 4.32e−07; B ***p = 1.73e−06), while upregulated groups (D and E) show a slight but significant increase (D *p = 0.03; E *p = 0.04). Only maternally downregulated group A and paternally upregulated group E show significant changes in ATAC-seq (A ***p = 0.0001; B ***p = 0.001) at paternal alleles. F UCSC Genome browser (GRCm38/mm10) view of paternal H3K27me3 and chromatin accessibility profiles in wt (−) and Kdm6aΔE1 ( +) at the paternally downregulated Neurog3 gene shows increased H3K27me3 but no corresponding decrease in ATAC-seq around the promoter. G Same analysis as in (A, B) but in the CB Kdm6aΔE2.5 clone. Only maternally downregulated genes (group A) show increased H3K27me3. There were no significant ATAC-seq changes. H Same analysis as in (D, E) but in the CB Kdm6aΔE2.5 clone. Maternally downregulated group A show increased H3K27me3, while ATAC-seq changes were only seen on paternal alleles. Group A includes genes downregulated on the maternal allele and group B on the paternal allele. Group D includes genes upregulated on the maternal allele and group E, on the paternal allele