Figure 6
Figure 6. Comparative analysis of genome-wide GABPα occupancy and expression profiles by GSEA broadens GABP direct target genes/pathways. (A) GSEA profile of correlation between GABP-regulated genes and GABP-bound gene set. GABP-activated direct targets are at the leading edge of positive correlation (in red box on the left), and GABP-repressed direct targets are at the leading edge of negative correlation (in blue box on the right). Functional annotation of these 2 subsets is summarized in supplemental Table 3. (B) Downstream transcription factors that are regulated by both GABP and Scl/Tal1. Shown is the heatmap with color-coded scale bars showing Z-scores. (C) GSEA profiles of correlation between genes positively regulated by GABP and gene sets containing stem cell signatures. (D) GSEA profile of correlation between genes negatively regulated by GABP and a gene set containing genes enriched in mature blood cells compared with HSCs (shared between fetal liver and adult BM HSCs). Other negatively correlated gene sets include HSC_MATURE_FETAL (P = 0, false discovery rate [FDR] q = 0.009) and HSC_MATURE_ADULT (P = 0, FDR q = 0.069) in GSEA, containing genes up-regulated in mature blood cells compared with fetal liver and BM HSCs, respectively (both from Ivanova et al38). (E) GSEA profiles of correlation between genes positively regulated by GABP and gene sets of select pathways. For all the GSEA in panels A and C-E, enrichment plots are shown, with gene set names, nominal P values, and FDR q values marked on top of the plots. More detailed description of all the gene sets in panels C through E, genes at the leading edge, and heatmaps are given in supplemental Figure 3. Note that a reported P = 0 indicates an actual P < 1/number of permutations. In our analysis the number of permutations was set at 1000, and thus the reported “P = 0” is equivalent to P < .001.

Comparative analysis of genome-wide GABPα occupancy and expression profiles by GSEA broadens GABP direct target genes/pathways. (A) GSEA profile of correlation between GABP-regulated genes and GABP-bound gene set. GABP-activated direct targets are at the leading edge of positive correlation (in red box on the left), and GABP-repressed direct targets are at the leading edge of negative correlation (in blue box on the right). Functional annotation of these 2 subsets is summarized in supplemental Table 3. (B) Downstream transcription factors that are regulated by both GABP and Scl/Tal1. Shown is the heatmap with color-coded scale bars showing Z-scores. (C) GSEA profiles of correlation between genes positively regulated by GABP and gene sets containing stem cell signatures. (D) GSEA profile of correlation between genes negatively regulated by GABP and a gene set containing genes enriched in mature blood cells compared with HSCs (shared between fetal liver and adult BM HSCs). Other negatively correlated gene sets include HSC_MATURE_FETAL (P = 0, false discovery rate [FDR] q = 0.009) and HSC_MATURE_ADULT (P = 0, FDR q = 0.069) in GSEA, containing genes up-regulated in mature blood cells compared with fetal liver and BM HSCs, respectively (both from Ivanova et al38 ). (E) GSEA profiles of correlation between genes positively regulated by GABP and gene sets of select pathways. For all the GSEA in panels A and C-E, enrichment plots are shown, with gene set names, nominal P values, and FDR q values marked on top of the plots. More detailed description of all the gene sets in panels C through E, genes at the leading edge, and heatmaps are given in supplemental Figure 3. Note that a reported P = 0 indicates an actual P < 1/number of permutations. In our analysis the number of permutations was set at 1000, and thus the reported “P = 0” is equivalent to P < .001.

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