Fig. 5: Loss of Hdac1 selectively perturbs cell-type-specific transcription. | Leukemia

Fig. 5: Loss of Hdac1 selectively perturbs cell-type-specific transcription.

From: HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy

Fig. 5

A Schematic representation of ATAC- and RNA-seq experiments. ATAC- and RNA-seq were performed in parallel using end-stage thymic tumors from NPM::ALK mice (biological replicates n = 4, blue) and NPM::ALK Hdac1KO mice (biological replicates n = 4, red). ATAC- and RNA-seq were correlated with topologically associating domains (TADs) inferred from publicly available HiC data [40]. B Principal Component Analysis (PCA) of ATAC-seq data illustrating the similarity/variance of NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples. C Violin plot showing the distribution of peak sizes and the average number of peaks in NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples based on ATAC-seq analyses. D Venn diagram depicting shared and unique open chromatin regions (=peaks) between NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples. E Bar charts representing the number and percentages of overall and statistically significant (p < 0.05) correlations between RNA- and ATAC-seq data (upper), as well as the number and percentage of negative and positive correlations among the statistically significant (p < 0.05) correlations (lower). F Stacked bar chart representing the percentage of open chromatin regions located in different genomic regions, according to the legend on the right side, comparing the open chromatin regions that are positively correlated (p < 0.05) with changes in gene expression (e.g., open chromatin in promoter region leads to higher gene expression) (upper) and open chromatin regions that are negatively correlated (p < 0.05) with changes in gene expression (e.g., open chromatin in promoter region leads to lower gene expression) (lower). G Bubble chart representing significantly enriched pathways in NPM::ALK Hdac1KO end-stage thymic tumors as compared to NPM::ALK end-stage thymic tumors based on Ingenuity Pathway Analysis (IPA®) of upregulated genes (RNA-seq: |LFC| ≥ 1, adj p < 0.05) that were correlated with changes in chromatin accessibility (correlation p < 0.5). The size of the circles represents the number of genes affected within a given pathway, the color indicates the significance level based on the gradient scheme on the right. H Immunoblot showing protein levels of CD3d, CD3g and CD3e in end-stage thymic tumors excised from NPM::ALK (n = 4), NPM::ALK Hdac1KO (n = 4) and NPM::ALK Hdac1KI mice (n = 4). Beta-actin was used as a loading control. The numbers on the left indicate the molecular weight of analyzed proteins in kiloDalton (kDa). I VST (variance stabilizing transformation) normalized counts based on RNA-seq analysis for Cd3g, Cd3d, and Cd3e comparing NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples.

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