The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans
- Maria C. Ow1,
- Natalia J. Martinez1,2,
- Philip H. Olsen3,
- Howard S. Silverman3,
- M. Inmaculada Barrasa1,2,
- Barbara Conradt3,
- Albertha J.M. Walhout1,2, and
- Victor Ambros1,4
- 1 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 2 Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 3 Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally via antisense base-pairing. Although miRNAs are involved in a variety of important biological functions, little is known about their transcriptional regulation. Using yeast one-hybrid assays, we identified transcription factors with a FLYWCH Zn-finger DNA-binding domain that bind to the promoters of several Caenorhabditis elegans miRNA genes. The products of the flh-1 and flh-2 genes function redundantly to repress embryonic expression of lin-4, mir-48, and mir-241, miRNA genes that are normally expressed only post-embryonically. Although single mutations in either flh-1 or flh-2 genes result in a viable phenotype, double mutation of flh-1 and flh-2 results in early larval lethality and an enhanced derepression of their target miRNAs in embryos. Double mutations in flh-2 and a third FLYWCH Zn-finger-containing transcription factor, flh-3, also result in enhanced precocious expression of target miRNAs. Mutations of lin-4 or mir-48&mir-241 do not rescue the lethal flh-1; flh-2 double-mutant phenotype, suggesting that the inviability is not solely the result of precocious expression of these miRNAs. Therefore, the FLH-1 and FLH-2 proteins likely play a more general role in regulating gene expression in embryos.
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Footnotes
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↵4 Corresponding author.
↵4 E-MAIL victor.ambros{at}umassmed.edu; FAX (508) 856-5657.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1678808.
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- Received March 27, 2008.
- Accepted July 21, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press