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Fetal globin expression is regulated by Friend of Prmt1.

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

SUBMITTER: van Dijk TB

PROVIDER: S-EPMC2993632 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Fetal globin expression is regulated by Friend of Prmt1.

van Dijk Thamar Bryn TB Gillemans Nynke N Pourfarzad Farzin F van Lom Kirsten K von Lindern Marieke M Grosveld Frank F Philipsen Sjaak S

Blood 20100805 20

An estimated 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; α2β(S)2). Therefore, understanding the molecular mechanism of globin s ...[more]

PMID: 20688955

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