title: A GATA-1-regulated microRNA locus essential for erythropoiesis.
abstract: MicroRNAs (miRNAs) control tissue development, but their mechanism of regulation is not well understood. We used a gene complementation strategy combined with microarray screening to identify miRNAs involved in the formation of erythroid (red blood) cells. Two conserved miRNAs, miR 144 and miR 451, emerged as direct targets of the critical hematopoietic transcription factor GATA-1. In vivo, GATA-1 binds a distal upstream regulatory element to activate RNA polymerase II-mediated transcription of a single common precursor RNA (pri-miRNA) encoding both mature miRNAs. Zebrafish embryos depleted of miR 451 by using antisense morpholinos form erythroid precursors, but their development into mature circulating red blood cells is strongly and specifically impaired. These results reveal a miRNA locus that is required for erythropoiesis and uncover a new regulatory axis through which GATA-1 controls this process.
authors.affiliation: Division of Hematology, Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Dore
authors.forename: Julio D
authors.initials: JD
authors.lastname: Amigo
authors.forename: Camila O
authors.initials: CO
authors.lastname: Dos Santos
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gai
authors.forename: John W
authors.initials: JW
authors.lastname: Tobias
authors.forename: Duonan
authors.initials: D
authors.lastname: Yu
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Klein
authors.forename: Christine
authors.initials: C
authors.lastname: Dorman
authors.forename: Weisheng
authors.initials: W
authors.lastname: Wu
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
authors.forename: Barry H
authors.initials: BH
authors.lastname: Paw
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015672:Erythroid Precursor Cells / Q000166:cytology*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D046228:Microarray Analysis; D015027:Zebrafish
chemical_list: D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D035683:MicroRNAs