KLF1 regulates genes involved in cell-cycle control, cytokinesis, autophagy, globin synthesis, and cell signaling. Screen captures from the UCSC Genome Browser (hg19) with RefSeq transcripts for gene(s) at the top (blue) and the direction of transcription shown by arrowheads. All alternative transcripts from the RefSeq repository are included. Coding exons have an expanded vertical height compared with noncoding (5′ or 3′ untranslated region) per UCSC custom. The wiggle tracks for mapped and aligned RNA-seq tags are shown for the proband (KLF1 null, red) and orthochromatic erythroblasts (Ortho, green).³⁶  Tags are highly enriched over exons as expected for polyA⁺ RNA-seq libraries. The top of the vertical scale for orthochromatic erythroblasts (tag counts) at each gene varies from 80 to 20 000, which reflects the broad range of gene expression detectable by RNA-seq (refer to supplemental Table 1 for FPKM values). The scale for the KLF1 RNA-seq track is 4 times lower to amplify its height to provide a “normalized” comparison with the green track (see Methods). Wiggle tracks for ChIP-seq data for KLF1 and input DNA (black) were uploaded from GEO.³⁷  The wiggle track for DNase 1 HS-seq data from K562 cells generated by the ENCODE consortium (see Methods) was uploaded to show likely promoter and enhancer sites (bottom track, navy). KLF1 directly regulates expression of E2F2 (A), KIF23 (B), ATG4D (C), AHSP (D), and DYRK3 (E). The 5 genes are poorly expressed in the proband (red tracks) compared with orthochromatic erythroblasts (green tracks). ChIP-seq peaks at the promoter (pr) and 2 first intron enhancer sites (en1 and en2) are identical to previously described Klf1-occupied sites in the murine E2f2 gene.⁵¹  KLF1 binds the KIF23 promoter and a site ∼3 kb upstream, the ATG4D promoter and a site ∼1 kb upstream, the AHSP promoter, and the DYRK3 promoter and a site ∼3 kb upstream (black tracks). Most of these display erythroid DNAse1 hypersensitivity (blue track).