Fetal globin expression is regulated by Friend of Prmt1

An estimated 6% to 7% of the earth's population carries a mutation affecting red blood cell function. The beta-thalassemias and sickle cell disease are the most common monogenic disorders caused by these mutations. Increased levels of gamma-globin ameliorate the severity of these diseases because fetal hemoglobin (HbF; alpha 2 gamma 2) can effectively re-place adult hemoglobin (HbA; alpha 2 beta 2) and counteract polymerization of sickle hemoglobin (HbS; alpha 2 beta(S)2). 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 gamma-globin gene expression. Knockdown of FOP in adult erythroid progenitors strongly induces HbF. Importantly, gamma-globin expression can be elevated in cells from beta-thalassemic patients by reducing FOP levels. These observations identify FOP as a novel therapeutic target in beta-hemoglobinopathies. (Blood. 2010;116(20):4349-4352)