Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells.
OBJECTIVE
MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription factors Ets-1 and Ets-2 regulate miR-126 expression.


RESULTS
A genomic region between -71 and -100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene.


CONCLUSIONS
Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects.
Harris
Tamia A
TA
Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yamakuchi
Munekazu
M
Kondo
Maiko
M
Oettgen
Peter
P
Lowenstein
Charles J
CJ
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D066255:EGF Family of Proteins; D042783:Endothelial Cells / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008156:Luciferases / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D050787:Proto-Oncogene Protein c-ets-2 / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D015533:Transcriptional Activation
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; C479627:Egfl7 protein, mouse; D016228:Endothelial Growth Factors; C527111:MIRN126 microRNA, human; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D011506:Proteins; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D008156:Luciferases