title: 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 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 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.
authors.affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. t.vandijk@erasmusmc.nl
authors.forename: Thamar Bryn
authors.initials: TB
authors.lastname: van Dijk
authors.forename: Nynke
authors.initials: N
authors.lastname: Gillemans
authors.forename: Farzin
authors.initials: F
authors.lastname: Pourfarzad
authors.forename: Kirsten
authors.initials: K
authors.lastname: van Lom
authors.forename: Marieke
authors.initials: M
authors.lastname: von Lindern
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C541075:CHTOP protein, human; C554294:FOP protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D005319:Fetal Hemoglobin