Fig. 3: NUP98::KDM5A actively maintains H3K27ac marks on target genes. | Nature Communications

Fig. 3: NUP98::KDM5A actively maintains H3K27ac marks on target genes.

From: Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12

Fig. 3

A H3K27ac ChIP-qPCR in dTAG-NUP98::KDM5A cells for Hoxa9 and Meis1 after treatment with dTAG13 for indicated time points compared to DMSO and a negative control genomic region (n = 2 technical replicates, mean ± SD). B Heatmaps and profile-plots of H3K27ac CUT&Tag data of dTAG13 (35 nM) and DMSO-treated dTAG-NUP98::KDM5A cells showing 161 significantly downregulated sites compared to 1000 random sites with no significant changes (n = 3, FDR < 0.05). C Representative tracks of H3K27ac CUT&Tag data (dTAG13 and DMSO). D Time-series plots showing cluster analysis of up and downregulated transcripts from RNA-seq data of dTAG-NUP98::KDM5A cells treated with dTAG13 (35 nM) for 8 h or 24 h compared to DMSO (0 h) (n = 4 biological replicates per time point). The upper and lower ends of the bars represent the minimum and maximum expression values for the respective group. The lines represent the mean expression profile across replicates for each group. E Heatmap of RNA-seq data in dTAG-NUP98::KDM5A cells after 8 h and 24 h of dTAG13 treatment compared to DMSO, showing 249 significantly differentially expressed genes at 24 h dTAG13 treatment (n = 4, log2FC > 1 or < −1, padj < 0.05, statistical analysis and p-value calculations were performed using DESeq2). F Scatter plot showing log2FC values in gene expression (QUANT-seq) and H3K27ac levels (CUT&Tag) upon dTAG13 treatment (35 nM, 8 h) compared to DMSO. G Hockey stick plot of H3K27ac CUT&Tag data in dTAG-NUP98::KDM5A cells (left). Genes are ranked according to normalized read signal, including a quantitative box plot representation (right, target genes n = 38, other genes n = 24,415, two-sided Wilcoxon rank sum test with continuity correction, p-value < 2.2e-16). Data are presented as boxplots where the center line represents the median, the bounds of the box indicate the first (25th percentile) and third (75th percentile) quartiles and the whiskers extend to 1.5 × inter-quartile range from the hinges. Data points beyond this range are shown as individual dots and represent outliers. Source data are provided as a Source Data file.

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