Fop regulates embryonic globin genes in mouse and human erythroid cells. Lentiviral-mediated knockdown of Fop in (A) mouse erythroid progenitor cells containing a single copy of the human globin locus (PAC8) and (B) primary HEP show the specific induction of mouse and human fetal β-like globin genes, as demonstrated by qualitative PCR analysis. Western blot analysis was used to validate Fop knockdown levels (bottom panels). (C) Quantitative S1 nuclease protection assay and Western blot analysis demonstrate significant γ-globin reactivation in HEP cells with reduced FOP expression. (D) Globin high-performance liquid chromatography of transduced HEP cells after 11 days of culture. Peaks for HbA (α2β2), HbA2 (α2δ2), and HbF (α2γ2) are indicated. (E) The shRNA-mediated knockdown of FOP increases HbF levels on average approximately 3.7 times in cultured human erythroid progenitor cells. Cultures from 3 independent healthy donors were analyzed. ns indicates not significant. *Significant difference (Mann-Whitney test, P < .05).