A GATA-1-regulated microRNA locus essential for erythropoiesis.
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.
Dore
Louis C
LC
Division of Hematology, Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Amigo
Julio D
JD
Dos Santos
Camila O
CO
Zhang
Zhe
Z
Gai
Xiaowu
X
Tobias
John W
JW
Yu
Duonan
D
Klein
Alyssa M
AM
Dorman
Christine
C
Wu
Weisheng
W
Hardison
Ross C
RC
Paw
Barry H
BH
Weiss
Mitchell J
MJ
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
D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D035683:MicroRNAs