Results of ChIP-seq analysis for H3K27me3, KMT2D, and SMARCA4. (A) Venn diagram showing the overlap of statistically significant peaks of H3K27me3 between Utx^+/+ and Utx^Δ/Δ LSKs. (B) Gene ontology (GO) enrichment analysis of the genes with H3K27me3 peaks in Utx^Δ/Δ LSKs with the Genomic Regions Enrichment of Annotations Tool (GREAT). The ranks were calculated by P values. (C) Pathway analysis of the genomic regions with H3K27me3 peaks in Utx^Δ/Δ LSKs with Enrichr_TRANSFAC and JASPAR position weight matrice (PWM) databases. TGF-β downstream transcription factors are shown in red. (D) SMAD proteins SMAD3, SMAD2, and SMAD4, detected from transcription factor motif analysis of the genomic regions with H3K27me3 peaks in Utx^Δ/Δ LSKs with Homer Known Motif Enrichment Results. (E) Venn diagram (left) showing the overlap between genes downregulated (Log₂FC < −0.5) by Utx deficiency and those with elevated H3K27me3 peaks around annotated TSS ± 5 kb by Utx deficiency. The overlay of H3K27me3 peaks at the representative TGF-β signaling-associated gene loci (right), Hnf4a and Col1a1, in Utx^+/+ and Utx^Δ/Δ LSKs. Remarkable H3K27me3 peaks in Utx^Δ/Δ LSKs are outlined in red. (F) Venn diagrams showing the overlap between upregulated (Log₂FC > 0.5) genes in Utx^Δ/Δ LSKs and Aging Up Top200 (Up genes, left) and the overlap between downregulated (Log₂FC < −0.5) genes in Utx^Δ/Δ LSKs and Aging Down Top200 (Down genes, right). (G) Bar graph (left) showing the percentage of KMT2D binding (TSS ± 5 kb) of Up and Down genes in at least 1 of the published ChIP-seq data sets of mouse blood tissues available in the ChIP Atlas,⁶¹  GSE69162,⁶²  and GSE 103508.⁶²  The bigwig files and bed files were obtained from the ChIP Atlas. The significance threshold for significant peaks is defined as q < 1 × 10⁻¹⁰. Overlay of KMT2D peaks at the indicated Down gene loci as representative images (right). Remarkable KMT2D peaks are outlined in red. (H) Histogram (left) showing the percentage of genes bound to SMARCA4 (TSS ± 5 kb) in Up or Down genes in at least 1 of the published ChIP-seq data sets of mouse blood tissues available in ChIP-Atlas,⁶¹  GSE23719,⁶⁴  GSE79391,⁶⁴  GSE82144,⁶⁸  GSE52279,⁶⁵  and GSE66978.⁶⁶  The bigwig files and bed files were obtained from the ChIP-Atlas. Significance threshold for significant peaks is defined as q < 1 × 10⁻¹⁰. The columns indicate the percentages of Up genes, Down genes, KMT2D peak-positive genes with SMARCA4 peaks, respectively. The number of the horizontal axis shows the overlap of SMARCA4 peaks from different data sets. The overlay of SMARCA4 and KMT2D peaks (TSS ± 5 kb) at the indicated Down genes loci in which SMARCA4 peaks were observed in 3 data sets and a KMT2D peak was overlapped with ≥1 SMARCA4 peaks (right).