Work

IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts

Year: 2017

Type: article

Abstract: Significance Fetal hemoglobin (HbF) expression is a tissue- and stage-specific marker of ontogeny in large mammals, which also has therapeutic importance for beta hemoglobinopathies. The heterochronic let-7 miRNAs, which regulate the time and sequence of stage-specific developmental events, have also been shown to regulate HbF in adult human erythroblasts. Here we provide a focused investigation of a let-7 target named “insulin-like growth-factor 2 mRNA-binding protein 1” (IGF2BP1), for its potential role in reactivating HbF in adult cells. IGF2BP1 overexpression caused robust increases of HbF and a reversal from the adult toward a fetal-like globin phenotype. IGF2BP1 effects are partially mediated by posttranscriptional regulation of the known HbF regulator BCL11A. These results suggest a novel mechanism for the regulation of BCL11A and HbF in humans.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1609552114