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. 2019 May 3;8:e44306. doi: 10.7554/eLife.44306

Figure 4. HDAC inhibitors epigenetically disrupt PAX8 transcription.

(A) ChIPseq profiles for H3K27ac occupancy of PAX8 gene locus in KURAMOCHI, SKOV3 and COV 413B cells. The x-axis showed gene tracks, and the y-axis showed the signal of H3K27ac binding within 50 bp bins in units of reads per million bin (rpm/bin). (B) ChIP-qPCR quantification of H3K27ac relative enrichment in PAX8 promoter or intron regions as compared to input signals. Each column represented the mean value of three biological replicates, and error bars indicated standard deviation. (C) Quantitative PCR analysis of PAX8 gene expression in KURAMOCHI, SKOV3 and COV 413B cells treated with panobinostat (100 nM) or romidepsin (50 nM). Each column represented the mean value of three biological replicates, and error bars indicated standard deviation. (D) Heatmaps of PAX8 regulon gene expression in KURAMOCHI cells as measured by RNAseq. (E) Principal component analysis (PCA) of RNAseq data in KURAMOCHI cells with HDAC treatment or PAX8 depletion. (F) Gene ontology categories and KEGG pathways overrepresented in differentially expressed transcripts that were inhibited upon HDAC treatment or PAX8 depletion in KURAMOCHI cells. (G) GSEA plots indicated downregulation of PAX8 gene signature upon HDAC treatment in KURAMOCHI cells.

Figure 4.

Figure 4—figure supplement 1. HDAC inhibitors altered H3K27ac distribution and resulted in rapid downregulation of PAX8.

Figure 4—figure supplement 1.

(A) ChIPseq profiles for H3K27ac occupancy of PAX8 gene locus in KURAMOCHI cells treated with DMSO, panobinostat or romidepsin. The x-axis showed gene tracks, and the y-axis showed the signal of H3K27ac binding. (B) The log2 change in gene expression after indicated drug treatment over time for expressed transcripts (FPKM +1 > 10) in KURAMOCHI cells. Each line represented a single gene with PAX8 drawn in red. (C) Heatmaps of RNAseq data for HDAC-inhibited or PAX8-depleted KURAMOCHI cells.
Figure 4—figure supplement 2. HDAC inhibitors suppressed lineage survival oncogenes expression and cell proliferation in lung cancer.

Figure 4—figure supplement 2.

(A) Relative gene expression levels in indicated lung cancer cells treated with panobinostat (100 nM) or romidepsin (50 nM). (B) Indicated lung cancer cells were treated with panobinostat or romidepsin, and analyzed by crystal violet staining.