The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans.
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.
Ow
Maria C
MC
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Martinez
Natalia J
NJ
Olsen
Philip H
PH
Silverman
Howard S
HS
Barrasa
M Inmaculada
MI
Conradt
Barbara
B
Walhout
Albertha J M
AJ
Ambros
Victor
V
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D035683:MicroRNAs; D014157:Transcription Factors
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