Anestimated 6% to 7% of the earth's population carries a mutation affecting red blood cell function. The β-thalassemias and sickle cell disease are the most common monogenic disorders caused by these mutations. Increased levels of γ-globin ameliorate the severity of these diseases because fetal hemoglobin (HbF; α2γ2) can effectively replace adult hemoglobin (HbA; α2β2) and counteract polymerization of sickle hemoglobin (HbS;α2βS2). Therefore, understanding the molecular mechanism of globin switching is of biologic and clinical importance. Here, we show that the recently identified chromatin factor Friend of Prmt1 (FOP) is a critical modulator of γ-globin gene expression. Knockdown of FOP in adult erythroid progenitors strongly induces HbF. Importantly, γ-globin expression can be elevated in cells from β-thalassemic patients by reducing FOP levels. These observations identify FOP as a novel therapeutic target in β-hemoglobinopathies.

Additional Metadata
Persistent URL dx.doi.org/10.1182/blood-2010-03-274399, hdl.handle.net/1765/21808
Citation
van Dijk, T.B., Gillemans, N., Pourfarzad, F., F., van Lom, K., von Lindern, M.M., & Grosveld, F.G.. (2010). Fetal globin expression is regulated by Friend of Prmt1. Blood, 116(20), 4349–4352. doi:10.1182/blood-2010-03-274399