human chronic myelogenous leukemia cell line k562  (ATCC)

Journal: Science Advances

Article Title: Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators

doi: 10.1126/sciadv.adu8292

Figure Lengend Snippet: ( A ) Venn diagrams showing the overlap of genes with CEs, CE circles, with the DEGs, DE circles, per genotype as compared to WT samples. ( B ) Venn diagram showing the enrichment of DNA binding protein motifs at the promoters of the DEGs. ( C ) Bubble plot showing the enrichment of DNA binding proteins unique to the double-mutant expression signature and interacting with genes with CEs. The binary matrix on the right side shows which protein (row of the heatmap) physically interacts with which protein coded in a mis-spliced gene (columns of the matrix). ( D ) Bar plot showing the percentage of DNA binding proteins interacting with proteins that contain CEs. ( E ) Bar plot showing the number of chromatin modifiers found with CEs at each genotype. ( F ) Bar plot showing the relative survival of K562 cells carrying IDH2 R140Q and/or SRSF2 P95H mutations in response to treatment with different doses of romidepsin. Asterisks indicate statistical significance [ P adj < 0.05 as per analysis of variance (ANOVA) followed by Tukey’s post hoc; shown are only the significant results with respect to the double mutant; N = 3 replicates]. ( G ) Graphical summary of the results of our whole study. Mutations in both IDH2 and SRSF2 genes cause the abnormal promotion of CCNG-rich exons, which code for proteins physically interacting with TFs or complexes that, in turn, regulate the expression of downstream genes, including signaling genes.

Article Snippet: The K562 human myeloid leukemia cell line was purchased from American Type Culture Collection (ATCC; #CCL-243).

Techniques: Binding Assay, DNA Binding Assay, Mutagenesis, Expressing