The human and mouse extended α-globin loci. (A) Human and (B) mouse α-globin gene clusters are diagrammed. The major adult-expressed genes are indicated with blue font. Corresponding transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) peaks indicate open chromatin in adult RBC precursors. Enhancer modules associated with open chromatin (ATAC-seq signal) are indicated as multispecies conserved sequence (MCS) R1-R4 (human) or R1, R2, R3, Rm, and R4 (mouse). Human HBA2 is nearest to the enhancer and is expressed at twofold- to fivefold-higher levels than HBA1 in adult RBCs. Similarly, mouse Hba-a1 is nearest to the enhancer and is expressed at twofold- to threefold-higher levels than Hba-a2 in adult RBCs. The common α-thalassemia deletion, −α3.7 shown at the bottom of panel A generates a single α-globin fusion gene.