Figure 2.
Genome editing to increase HbF production. Only HBG2 and its upstream binding sites for BCL11A and ZBTB7A are depicted. The expression of BCL11A, 1 of 2 major repressors of HbF gene expression, is controlled by an erythroid-specific enhancer. BCL11A binds to a TGACCA motif centered at position −115 in the promoters of both HBG2 and HBG1. ZBTB7A, the other major HbF gene repressor, not shown, binds at positions −195 to −197 and −201 to −202 upstream of both γ-globin genes. A still unknown transcription factor(s) is likely to bind the −158 site. The −158 polymorphism is found only in HBG2. CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer, shown as a double-strand break, or its binding sites in the HbF gene promoters, shown before editing, reverses the repression of these genes increasing HbF.

Genome editing to increase HbF production. Only HBG2 and its upstream binding sites for BCL11A and ZBTB7A are depicted. The expression of BCL11A, 1 of 2 major repressors of HbF gene expression, is controlled by an erythroid-specific enhancer. BCL11A binds to a TGACCA motif centered at position −115 in the promoters of both HBG2 and HBG1. ZBTB7A, the other major HbF gene repressor, not shown, binds at positions −195 to −197 and −201 to −202 upstream of both γ-globin genes. A still unknown transcription factor(s) is likely to bind the −158 site. The −158 polymorphism is found only in HBG2. CRISPR-Cas9 editing of either the BCL11A erythroid-specific enhancer, shown as a double-strand break, or its binding sites in the HbF gene promoters, shown before editing, reverses the repression of these genes increasing HbF.

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