Genetic Interaction between Mutations in c-Myb and the KIX Domains of CBP and p300 Affects Multiple Blood Cell Lineages and Influences Both Gene Activation and Repression
Figure 4
Combined KIX domain and c-Myb haploinsufficiency synergistically affects multiple blood lineages.
Peripheral blood counts from 1-3 month old C57BL/6J x 129Sv F1 and C57BL/6J background mice. (A-G) Counts from automated Hemavet complete blood count. For B cells and T cells, total lymphocyte counts from complete blood count were parsed using flow cytometry to determine the percentage of lymphocytes that were positive for B220 (B cells), CD3 (T cells), CD4 and CD8 (T cell subsets). Asterisks indicate significant p value by pairwise Tukey post test following one way ANOVA (N=13-19 per genotype, * p<0.05, ** p<0.01, *** p<0.001). (H) Epistasis values and 95% confidence intervals calculated using five independent experiments with wild type, c-Myb+/-, p300+/KIX;CBP+/KIX and triple-het p300+/KIX;CBP+/KIX;c-Myb+/- mice represented in each. Zero indicates no epistasis or the lack of synergistic interaction between mutations [i.e. equality of the multiplicative phenotype (or additivity of log-transformed phenotype in this case) of the extreme (wild type and p300+/KIX;CBP+/KIX;c-Myb+/-) and intermediate genotypes (c-Myb+/- and p300+/KIX;CBP+/KIX)]. A positive epistasis value indicates a greater than multiplicative increased phenotype for the extreme genotype, a negative epistasis value indicates a greater than multiplicative decreased (aggravated) phenotype for the extreme genotype.