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Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3333-8. doi: 10.1073/pnas.0712312105. Epub 2008 Feb 26.

A GATA-1-regulated microRNA locus essential for erythropoiesis.

Author information

1
Division of Hematology, Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

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.

PMID:
18303114
PMCID:
PMC2265118
DOI:
10.1073/pnas.0712312105
[Indexed for MEDLINE]
Free PMC Article

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