ζ- and α-globin expression in primitive and definitive erythropoiesis. (A) The mouse α-globin cluster showing the enhancers, and the embryonic (ζ) and adult (α) genes flanked by insulators (yellow arrows in black circles), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) showing the pattern of chromatin accessibility during primitive erythropoiesis. The peaks on the ATAC-seq correspond to accessible chromatin. Note that the ζ-gene is accessible and expressed in primitive (embryonic) erythropoiesis as indicated in the yellow box. (B) Illustration showing the expression of α globin and ζ globin leading to production of embryonic Hbs (Gower I and II). Note the globin gene expression takes place within a non–membrane bound transcriptional hub (white area) in the nucleus. (C) The mouse α-globin cluster and ATAC-seq assay in definitive erythropoiesis. Note the absence of ζ-gene peak on the ATAC-seq (yellow box) in definitive erythropoiesis indicating the ζ-gene is silenced and may be sequestered outside of the transcriptional hub. (D) illustration showing the expression of α globin but absent ζ globin in definitive erythropoiesis. LRF and BCL11A both interact possibly via the nucleosome remodeling and deacetylation (NuRD) complex leading to ζ-globin hypoacetylation and silencing in definitive (fetal and adult) erythroid cells. Both BCL11A and LRF are positively regulated by KLF1.