RN-1 induces γ-globin synthesis by inducing PGC-1α. (A-B) QRT-PCR analyses quantify the fold change in LSD1 and PGC-1α mRNAs after normalization to the expression of Oaz1. (C) Diagrammatic representation of the gain-of-function PGC-1α experiment. Lin^– BM cells from SCD mice were induced to undergo terminal erythroid differentiation in vitro after infection with adenoviruses that forcibly expressed PGC-1α (Ad-PGC-1α) or GFP (Ad-GFP). (D) Western blots depict abundant expression of PGC-1α in infected Lin^– BM cells. (E-H) The relative fold change of γ-, β-, εy-, and βh1-globin mRNA abundances normalized to Oaz1 mRNA, respectively. (I) Schematic model depicting a simplified mechanism by which RN-1 may indirectly (as well as directly, Figure 6B) control fetal globin gene expression by inhibition of LSD1 activity.