Fig. 6: Loss of Hdac1 hyperactivates oncogenic transcription. | Leukemia

Fig. 6: Loss of Hdac1 hyperactivates oncogenic transcription.

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

Fig. 6

A ATAC-seq tracks downloaded from the UCSC Genome Browser [65] depicting peaks, which represent chromatin accessibility in the Jdp2 gene. Biological replicates of NPM::ALK end-stage thymic tumors (n = 4, blue) and of NPM::ALK Hdac1KO end-stage thymic tumors (n = 4, red) are shown. The Gencode track (Gencode VM23 release) is displayed below the ATAC-seq tracks, indicating different transcripts of the Jdp2 gene. Colored boxes on the bottom show ENCODE candidate Cis-Regulatory Elements (cCREs) combined from all available cell types (red promoter, orange proximal enhancer, yellow distal enhancer, blue CTCF binding sites). B VST normalized counts based on RNA-seq analysis for Jdp2 comparing NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples. C VST normalized counts based on RNA-seq analysis for Tnk2 comparing NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples. D ATAC-seq tracks for the Pdgfb gene as in A. E VST normalized counts based on RNA-seq analysis for Pdgfb comparing NPM::ALK (blue) and NPM::ALK Hdac1KO (red) samples. F Schematic representation of the PDGFRB/STAT5 signaling pathway. Green boxes indicate genes upregulated in NPM::ALK Hdac1KO tumors as compared to NPM::ALK tumors based on RNA-seq data. G Immunoblot showing protein levels of PDGFRb, STAT5a, STAT5b and pSTAT5 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). H Schematic representation of the Ca2+ signaling pathway. Green boxes indicate genes upregulated, red boxes indicate genes downregulated in NPM::ALK Hdac1KO tumors as compared to NPM::ALK tumors based on RNA-seq data. ER, endoplasmic reticulum. I Bar plot depicting the results of the Homer Motif analysis [66], indicating enrichment of the NFAT:AP1 motif in promoter peaks of NPM::ALK Hdac1KO samples (red) compared to NPM::ALK samples (blue) or control sequences (background) identified by ATAC-seq analysis. J Immunoblot showing protein levels of NFAT1 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).

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