PUBLICATION

A GATA-1-regulated microRNA locus essential for erythropoiesis

Authors
Dore, L.C., Amigo, J.D., Dos Santos, C.O., Zhang, Z., Gai, X., Tobias, J.W., Yu, D., Klein, A.M., Dorman, C., Wu, W., Hardison, R.C., Paw, B.H., and Weiss, M.J.
ID
ZDB-PUB-080309-23
Date
2008
Source
Proceedings of the National Academy of Sciences of the United States of America   105(9): 3333-3338 (Journal)
Registered Authors
Amigo, Julio, Paw, Barry
Keywords
erythrocyte, hematopoiesis, transcription factor, anemia, gene expression
MeSH Terms
  • Animals
  • Cell Line, Tumor
  • Erythroid Precursor Cells/cytology*
  • Erythroid-Specific DNA-Binding Factors
  • Erythropoiesis/genetics*
  • GATA1 Transcription Factor/physiology*
  • In Situ Hybridization
  • Mice
  • MicroRNAs/analysis
  • MicroRNAs/physiology*
  • Microarray Analysis
  • Zebrafish
PubMed
18303114 Full text @ Proc. Natl. Acad. Sci. 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping