Fig. 3

Schematic representation of GATA3 point mutations. (A) Protein structure of GATA3 and its mutations in T-ALL. All mutations on GATA3 are visualized on the upper area of the protein structure, and mutations in the N-finger domain identified in G2 are visualized in the lower area. (B) Boxplot of gene expression of GATA3 in each subtype. The dashed line represents the mean value of GATA3 in 707 T-ALLs. The P values are calculated by comparing with the mean gene expression of GATA3 using Wilcoxon rank-sum test. (C) Boxplot of count of GATA3WT and altered GATA3MUT reads in G2. P value is calculated using paired Wilcoxon rank-sum test. (D) Binding free energy (KJ/mol) reveals binding affinities of GATA3 (wild type, R276Q) protein and wrapping and bridging DNA sequence. (E) Volcano plot shows the differentially expressed genes between G2 (GATA3-mut) and GATA3WT T-ALL. Each dot represents one gene. Genes significantly up-regulated in G2 (GATA3-mut) are colored in red, and significantly down-regulated in G2 (GATA3-mut) in blue. (F, Left) Gene-expression level of predicted bridging genes in T-ALL patients with different GATA3 genotypes; (Right) the gene ontology results using up-regulated bridging genes in GATA3R276Q. (G) WISH results of rag1 RNA probes between GATA3WT- and GATA3R276Q-mRNA injected embryos at 4 dpf. The phenotypes are defined as four groups: high, normal, mild, and extremely low according to the rag1 RNA+ area in thymus. The percent is quantified (Right). P value is calculated using Fisher’s exact test. (H) WISH results of cmyb, αe-globin, and lyz RNA probes between GATA3WT- and GATA3R276Q -injected embryos at 4 dpf. P value is calculated using Wilcoxon rank-sum test. (I) qRT-PCR analysis of mRNA expression of the GATA3 downstream genes and rag1 in both GATA3WT- and GATA3R276Q-mRNA injected embryos at 4 dpf. The relative mRNA expressions are normalized to human GATA3. P values are calculated using Student's t test.