PEAR1 gene structure (chr1:156893731-156916434, GRCh38/hg38 Assembly). Exons are indicated by full blue boxes. The ATG codon is indicated at exon 1. The major PEAR1 transcript (ENST00000292357), translated into the full PEAR1 receptor, is indicated as “X” (in magenta). Two CpG islands are located in the gene (CGI1 and CGI2, depicted as green boxes on the left and right side, respectively; Location in chromosome 1: 156892430‐156893919 and 156907978‐156908857, GRCh38/hg38 Assembly). Rs12041331 (chr1:156899922, GRCh38/hg38 Assembly) is indicated in red. CpG islands are defined based on the formula described by Gardiner-Garden. H3K4Me1, H3K4Me3, and H3K27Ac profiles in HUVEC and K562 cell lines are displayed as colored overlayed histograms (light blue for HUVEC and purple for K562) in “auto-scale to data view” mode that takes the highest signal in the selected region as the 100% of the intensity and displays all other signals accordingly (data produced by the Bernstein Laboratory at the Broad Institute and the University of California, Santa Cruz and part of the ENCODE database). DNase Hypersensitivity 1 regions are displayed as gray to black boxes (from less to more open chromatin conformation). CTCF ChIP-seq data from HUVECs and K562 cell lines are depicted as colored histograms in full visualization and are normalized for immunoglobulin G signals (data produced by ENCODE). PEAR1 conservation across vertebrates is displayed as blue histograms at the bottom of the figure using the Vertebrate Multiz Alignment and Conservation (100 species) University of California, Santa Cruz track. “PCGI1” (also depicted as black box) refers to the region we analyzed for DNA methylation estimates in CD34+ HSCs into MK precursors and is better described in Figure 5. A yellow box (broken line) highlights the PCGI1 region that colocalizes with CTCF binding in HUVECs and shows conservation across different vertebrates. Exons 15 and 16 are indicated in brown and indicate the region used for RT-qPCR quantification of PEAR1 expression in the present study.