Spatial regulation of microRNA gene expression in the Drosophila embryo

Frédéric Biemar; Robert Zinzen; Matthew Ronshaugen; Victor Sementchenko; J Robert Manak; Michael S Levine

doi:10.1073/pnas.0507817102

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Spatial regulation of microRNA gene expression in the Drosophila embryo

Journal article

Open access

Peer reviewed

Spatial regulation of microRNA gene expression in the Drosophila embryo

Frédéric Biemar, Robert Zinzen, Matthew Ronshaugen, Victor Sementchenko, J Robert Manak and Michael S Levine

Proceedings of the National Academy of Sciences - PNAS, Vol.102(44), pp.15907-15911

11/01/2005

DOI: 10.1073/pnas.0507817102

PMCID: PMC1276093

PMID: 16249329

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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.

DNA-Binding Proteins - physiology

Drosophila melanogaster - embryology

RNA Precursors

Transcription Factors - physiology

Genes

Gene Expression Regulation, Developmental - genetics

Drosophila melanogaster - genetics

Tissue Distribution

Drosophila Proteins - physiology

Animals

Enhancer Elements, Genetic

Twist-Related Protein 1 - physiology

Embryo, Nonmammalian

Transcription, Genetic

Mesoderm - metabolism

MicroRNAs - genetics

Nuclear Proteins - physiology

Phosphoproteins - physiology

Details

Title: Subtitle: Spatial regulation of microRNA gene expression in the Drosophila embryo
Creators: Frédéric Biemar - Division of Genetics and Development, Department of Molecular Cell Biology, Center for Integrative Genomics, University of California, Berkeley, CA 94720, USA
Robert Zinzen
Matthew Ronshaugen
Victor Sementchenko
J Robert Manak
Michael S Levine
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.102(44), pp.15907-15911
DOI: 10.1073/pnas.0507817102
PMID: 16249329
PMCID: PMC1276093
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: United States
Grant note: GM34431 / NIGMS NIH HHS R01 GM034431 / NIGMS NIH HHS
Language: English
Date published: 11/01/2005
Academic Unit: Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9983992063202771

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