Figure 9.
Figure 9. Brd4 inhibition restores de-repression of PRC2 target genes. (a) Fold enrichment (ChIP/input) values of H3K27ac at the enhancer and the promoter regions in JAK2V617F/Ezh2Δ/Δ LK cells 2 wk after the completion of the JQ1 treatment. (b) A scatter plot showing the relationship of fold enrichment (ChIP/input) values of H3K27ac (TSS ± 2.0 kb of RefSeq genes) between DMSO- and JQ1-treated JAK2V617F/Ezh2Δ/Δ LK cells (the light diagonal line represents the borderlines for twofold changes in H3K27ac levels). (c) GSEA plot for the canonical PRC2 targets defined in Fig. 7 b comparing LSKs in JQ1-treated with DMSO-treated JAK2V617F/Ezh2Δ/Δ mice. (d) Venn diagrams showing overlaps between PRC2 target genes and JQ1 target genes, which were defined in b and are shown in Table S1. (e) Fold enrichment (ChIP/input) values of H3K27ac at the promoter regions of the canonical PRC2 target genes (defined in Fig. 7 b) in JAK2V617F/Ezh2Δ/Δ LK cells 2 wk after the completion of the JQ1 treatment. (f) ChIP-seq view of H3K27ac levels at the promoter region of Hmga2 in JQ1-treated or nontreated JAK2V617F/Ezh2Δ/Δ LK cells. (g) qRT-PCR analysis of the expression of Hmga2 in LSKs and MEPs isolated from DMSO-treated or JQ1-treated WT mice (n = 3) and JAK2V617F/Ezh2Δ/Δ mice (n = 3) 2 wk after the completion of the treatment. (h) GSEA plot for the MkPs signature genes described in Fig. 6 g comparing LSK cells from JQ1-treated and DMSO-treated JAK2V617F/Ezh2Δ/Δ mice. (i) GO biological process gene sets that were enriched more in JQ-treated LSK cells than in DMSO-treated LSK cells as determined by GSEA (gene sizes and FDR q-values are shown in the top and bottom x axes). (a and e) Boxes and whiskers show the mean and minimum to maximum. The asterisks show ***, P < 0.001 by the Student’s t test. (c, h, and i) The normalized enrichment score (NES), nominal p-value, and false discovery rate (FDR) q-value are indicated. (a–f, h, and i) Experiments used cells from two individual mice per group. (g) Bars and asterisks show the mean ± SEM and *, P < 0.05 by the Student’s t test; two independent experiments.

Brd4 inhibition restores de-repression of PRC2 target genes. (a) Fold enrichment (ChIP/input) values of H3K27ac at the enhancer and the promoter regions in JAK2V617F/Ezh2Δ/Δ LK cells 2 wk after the completion of the JQ1 treatment. (b) A scatter plot showing the relationship of fold enrichment (ChIP/input) values of H3K27ac (TSS ± 2.0 kb of RefSeq genes) between DMSO- and JQ1-treated JAK2V617F/Ezh2Δ/Δ LK cells (the light diagonal line represents the borderlines for twofold changes in H3K27ac levels). (c) GSEA plot for the canonical PRC2 targets defined in Fig. 7 b comparing LSKs in JQ1-treated with DMSO-treated JAK2V617F/Ezh2Δ/Δ mice. (d) Venn diagrams showing overlaps between PRC2 target genes and JQ1 target genes, which were defined in b and are shown in Table S1. (e) Fold enrichment (ChIP/input) values of H3K27ac at the promoter regions of the canonical PRC2 target genes (defined in Fig. 7 b) in JAK2V617F/Ezh2Δ/Δ LK cells 2 wk after the completion of the JQ1 treatment. (f) ChIP-seq view of H3K27ac levels at the promoter region of Hmga2 in JQ1-treated or nontreated JAK2V617F/Ezh2Δ/Δ LK cells. (g) qRT-PCR analysis of the expression of Hmga2 in LSKs and MEPs isolated from DMSO-treated or JQ1-treated WT mice (n = 3) and JAK2V617F/Ezh2Δ/Δ mice (n = 3) 2 wk after the completion of the treatment. (h) GSEA plot for the MkPs signature genes described in Fig. 6 g comparing LSK cells from JQ1-treated and DMSO-treated JAK2V617F/Ezh2Δ/Δ mice. (i) GO biological process gene sets that were enriched more in JQ-treated LSK cells than in DMSO-treated LSK cells as determined by GSEA (gene sizes and FDR q-values are shown in the top and bottom x axes). (a and e) Boxes and whiskers show the mean and minimum to maximum. The asterisks show ***, P < 0.001 by the Student’s t test. (c, h, and i) The normalized enrichment score (NES), nominal p-value, and false discovery rate (FDR) q-value are indicated. (a–f, h, and i) Experiments used cells from two individual mice per group. (g) Bars and asterisks show the mean ± SEM and *, P < 0.05 by the Student’s t test; two independent experiments.

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