Emerging network of γ-globin regulators in adult life and prospective targets for therapeutic induction of HbF. Targets identified in the emerging network of HbF regulation include the KLF1, BCL11A, and MYB genes and the TR2/TR4 nuclear receptors that associate with corepressors DNA methyltransferase 1 (DNMT1) and lysine-specific demethylase 1 (LSD1). KLF1 has a dual role in the silencing of γ-globin genes: it activates BCL11A, a repressor of γ-globin gene expression, and it also activates the β-globin gene directly. BCL11A interacts with the GATA1, FOG1, and SOX6 erythroid transcription factors and with the NuRD deacetylase and remodeling complex to promote suppression of γ-globin gene expression. The nuclear receptors TR2/TR4 associate with corepressors DNMT1 and LSD1 as part of the DRED complex, a known repressor of embryonic and fetal globin genes in adults. MYB contributes to HbF regulation via activation of KLF1 (which activates BCL11A), activation of the DRED complex, and by modulating the number of F cells as part of its effect on erythroid differentiation kinetics and its pleiotropic effect on hematopoiesis.