Contrasting epigenetic landscape of α- and β- globin loci. In the silent, nonexpressed state (nonerythroid cells), the α-globin locus (red dot) is in open chromatin environment, whereas the β-globin locus (yellow dot) is in a closed chromatin conformation incorporated into heterochromatin (dark blue circle within the nucleus). The promoter of α-globin is unmethylated, bound by PRC2, and the associated histone has the H3K27me3 modification. In contrast, the β-globin locus is heavily methylated and does not show binding of PRC2 or the H3K27me3 chromatin modification. In the active state (erythroid cells), both loci are located away from heterochromatin and form loop structures to facilitate respective enhancer–promoter interactions, and both promoters show H3K4me3 active chromatin modification. However, only in the α-globin locus, PRC2 is detached and JMJD3 is recruited to facilitate removal of the H3K27me3 repressive chromatin modification.