title: Spatial regulation of microRNA gene expression in the Drosophila embryo.
abstract: MicroRNAs (miRNAs) regulate posttranscriptional gene activity by binding to specific sequences in the 3' UTRs of target mRNAs. A number of metazoan miRNAs have been shown to exhibit tissue-specific patterns of expression. Here, we investigate the possibility that localized expression is mediated by tissue-specific enhancers, comparable to those seen for protein-coding genes. Two miRNA loci in Drosophila melanogaster are investigated, the mir-309-6 polycistron (8-miR) and the mir-1 gene. The 8-miR locus contains a cluster of eight distinct miRNAs that are transcribed in a common precursor RNA. The 8-miR primary transcript displays a dynamic pattern of expression in early embryos, including repression at the anterior and posterior poles. An 800-bp 5' enhancer was identified that recapitulates this complex pattern when attached to a RNA polymerase II core promoter fused to a lacZ-reporter gene. The miR-1 locus is specifically expressed in the mesoderm of gastrulating embryos. Bioinformatics methods were used to identify a mesoderm-specific enhancer located approximately 5 kb 5' of the miR-1 transcription unit. Evidence is presented that the 8-miR enhancer is regulated by the localized Huckebein repressor, whereas miR-1 is activated by Dorsal and Twist. These results provide evidence that restricted activities of the 8-miR and miR-1 miRNAs are mediated by classical tissue-specific enhancers.
authors.affiliation: Division of Genetics and Development, Department of Molecular Cell Biology, Center for Integrative Genomics, University of California, Berkeley, CA 94720, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Biemar
authors.forename: Robert
authors.initials: R
authors.lastname: Zinzen
authors.forename: Matthew
authors.initials: M
authors.lastname: Ronshaugen
authors.forename: Victor
authors.initials: V
authors.lastname: Sementchenko
authors.forename: J Robert
authors.initials: JR
authors.lastname: Manak
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005796:Genes; D008648:Mesoderm / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009687:Nuclear Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D012322:RNA Precursors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C087725:Hkb protein, Drosophila; D035683:MicroRNAs; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012322:RNA Precursors; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C062236:dl protein, Drosophila