Engineered expression of fetal forms of hemoglobin has potential therapeutic use in treating individuals with hemoglobinopathies, for whom elevated expression of fetal globin in adulthood is beneficial. Now, Gerd Blobel and colleagues report that fetal globin expression can be reactivated in mouse and human adult erythroblasts through forced chromatin looping by an engineered zinc-finger (ZF) protein (Cell 158, 849–860, 2014). The authors created a custom ZF protein that binds to mouse embryonic globin promoter sequences. They fused the ZF to the self-association domain (SA) of Ldb1, a transcription factor involved in the formation of loops between globin gene promoters and the locus control region (LCR), a distal enhancer that drives developmental expression of the globin genes. Expression of the ZF-SA protein in primary adult erythroblasts increased embryonic globin expression by almost 800-fold. The authors also used another engineered ZF-SA protein that binds to human fetal globin gene promoters and showed that it induces chromatin looping between the fetal globin gene promoter and the LCR and activates fetal globin expression in primary adult human erythroid cells.