Journal
BLOOD
Volume 116, Issue 20, Pages 4349-4352Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-03-274399
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Funding
- Netherlands Genomics Initiative, Erasmus MC [93518009, 296088]
- Landsteiner Foundation for Blood Transfusion Research [0615]
- Netherlands Scientific Organization [DN 82-294]
- Center for Biomedical Genetics
- European Union EUtracc consortium
- Division of Extramural Research Activities, National Heart, Lung, and Blood Institute [5 RO1 HL073455-04]
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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)
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