Tcf1 exerts a crucial regulatory function within distal Myc enhancers. (A) Integrative genomics viewer (IGV) profiles for Controls, N1IC, and N1IC Tcf7^Δ/Δ from ATAC-seq analysis performed on sorted murine LSKs for Myc promoter (left panel), NMe (red), and TMe (green) (right panel). Tracks were group-scaled. Schematic representation of genetic loci is depicted below the profiles. (B) TMe evolutionary conservation tree (left panel) and predicted ultraconserved transcription factor binding motifs in the TMe sequence (right panel). PhastCons conservation scores are indicated above the sites (score >0.5). (C) Schematic representation of lentiviral (LV) overexpression experiment using CD34⁺ human CB cells transduced with LV overexpressing NOTCH1 (red, n = 2). Cells were used for ATAC-seq analysis. ATAC-seq (GSM4743251 and GSM4743252) data sets from CD34⁺ human CB cells were used as Controls. (D) Enrichment of biological pathways from GO biological process collection in genes with induced proximal accessibility by human NOTCH1 and Controls CD34⁺ human CB cells. Top 10 pathways are shown from ontologies with an FDR ≤ 0.01. P values were calculated with Fisher's exact test. (E) TOBIAS footprint analysis NOTCH1 vs Controls. Pathway enrichment analysis from KEGG pathway catalog regulated by TCF1-confirmed footprint. Top 5 pathways are shown with corresponding FDR. The panel below represents IGV chromatin accessibility profiles for both experimental groups shown for IL2RΑ. Tracks were group-scaled; scaling is shown in the top left corner. Schematic representation of genetic loci is depicted below the profiles together with footprint analysis at TCF1-binding motif. (F) IGV chromatin accessibility profiles for TMe in human NOTCH1 and Controls CD34⁺ human CB cells. Tracks were group-scaled. (G) Flow cytometric-based analysis of intracellular TCF1 levels in NOTCH1 (red) and Controls (gray) CD34⁺ human CB cells.