Fig. 3: Chromatin accessibility landscape of iPSC-derived HSPCs.
From: Human iPSCs-based modeling unveils SETBP1 as a driver of chromatin rewiring in GATA2 deficiency
A Venn Diagram and ATAC-seq tracks illustrating open differentially accessible peaks (DAPs), defined by padj<0.05 and abs(log2FC > 0.5). Tracks for MEF2C, BAALC, GFI1 and MEIS1 loci. Display of the genomic interval exhibiting the highest logFC from the comparison of condition GSA versus condition P. ATAC-seq signal is color-coded by condition: P (black), G (light-blue), GS (blue), GA (navy-blue), and GSA (dark-blue), S (light-grey), and A (dark-grey). Annotated regulatory elements are indicated: strong-enhancer (orange), distal-enhancer (yellow) and promoter-TSS (red), Genehancer track of UCSC Genome Browser(hg38). Green-box marks genomic interval displayed for each gene locus. Differential chromatin accessibility was assessed using edgeR and limma. Count data were modeled with negative binomial distribution, and moderated t-tests. Reported two-sided p-values are adjusted for comparisons using Benjamini–Hochberg false discovery rate (FDR). B Venn Diagram illustrating closed DAPs, defined by padj<0.05 and abs(log2FC > 0.5). Tracks for GFI1B, GATA1 and ITGA2B, ERG1 loci. ATAC-seq signal is color-coded by condition: P (black), G (light-blue), GS (blue), GA (navy-blue), and GSA (dark-blue), S (light-grey), and A (dark-grey). Annotated regulatory elements are indicated: strong-enhancer (orange), distal-enhancer (yellow) and promoter-TSS (red), Genehancer track of UCSC Genome Browser(hg38). Purple-box marks genomic interval displayed for each gene locus. Differential chromatin accessibility was assessed using edgeR and limma. Count data were modeled with negative binomial distribution, and moderated t-tests. Reported two-sided p-values are adjusted for comparisons using Benjamini–Hochberg FDR. C (Top) HOMER motif analysis of open DAPs. Top 25 enriched transcription factor (TF) binding motifs are shown for DAPs across GA (left), GS (middle), and GSA (right) conditions versus P. Each motif is annotated by corresponding TF name, family and enrichment in p-value, as determined by HOMER. (Bottom) HOMER motif analysis of closed DAPs. Top 5 enriched TF binding motifs are shown for DAPs across GA (left), GS (middle), and GSA (right) conditions versus P. Each motif is annotated by corresponding TF name, family and enrichment in p-value, as determined by HOMER. Motif enrichment analysis was performed with HOMER (knownMotifs). Enrichment p-values were calculated using one-sided cumulative hypergeometric test, with comparisons corrected by Benjamini–Hochberg FDR. Source data are provided as a Source Data file. D GATA2-targets identified by ChIP-seq data reported by Fujiwara et al.59 crossed with DAPs in the GA, GS, and GSA intersection. (Top) Overlaping 18 out of 687 genes with GATA2-bound targets. (Bottom) Overlaping 229 out of 714 genes with GATA2-bound targets. P=Parental, G=GATA2 mutant, GS=GATA2-SETBP1 mutant, GA=GATA2-ASXL1 mutant, GSA=GATA2-SETBP1-ASXL1 mutant.
