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      Identification of candidate downstream genes for the homeodomain transcription factor Labial in Drosophila through oligonucleotide-array transcript imaging

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          Abstract

          Background:

          Homeotic genes are key developmental regulators that are highly conserved throughout evolution. Their encoded homeoproteins function as transcription factors to control a wide range of developmental processes. Although much is known about homeodomain-DNA interactions, only a small number of genes acting downstream of homeoproteins have been identified. Here we use a functional genomic approach to identify candidate target genes of the Drosophila homeodomain transcription factor Labial.

          Results:

          High-density oligonucleotide arrays with probe sets representing 1,513 identified and sequenced genes were used to analyze differential gene expression following labial overexpression in Drosophila embryos. We find significant expression level changes for 96 genes belonging to all functional classes represented on the array. In accordance with our experimental procedure, we expect that these genes are either direct or indirect targets of labial gene action. Among these genes, 48 were upregulated and 48 were downregulated following labial overexpression. This corresponds to 6.3% of the genes represented on the array. For a selection of these genes, we show that the data obtained with the oligonucleotide arrays are consistent with data obtained using quantitative RT-PCR.

          Conclusions:

          Our results identify a number of novel candidate downstream target genes for Labial, suggesting that this homeoprotein differentially regulates a limited and distinct set of embryonically expressed Drosophila genes.

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          Most cited references52

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          Comparative genomics of the eukaryotes.

          A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
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            Homeobox genes and axial patterning.

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              High density synthetic oligonucleotide arrays.

              Experimental genomics involves taking advantage of sequence information to investigate and understand the workings of genes, cells and organisms. We have developed an approach in which sequence information is used directly to design high-density, two-dimensional rays of synthetic oligonucleotides. The GeneChipe probe arrays are made using spatially patterned, light-directed combinatorial chemical synthesis and contain up to hundreds of thousands of different oligonucleotides on a small glass surface. The arrays have been designed and used for quantitative and highly parallel measurements of gene expression, to discover polymorphic loci and to detect the presence of thousands of alternative alleles. Here, we describe the fabrication of the arrays, their design and some specific applications to high-throughput genetic and cellular analysis.
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                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1465-6906
                1465-6914
                2001
                24 April 2001
                : 2
                : 5
                : research0015.1-research0015.9
                Affiliations
                [1 ]Institute of Zoology, Biocenter/Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
                [2 ]PRGT, Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland.
                Correspondence: Frank Hirth. E-mail: Frank.Hirth@unibas.ch
                Article
                gb-2001-2-5-research0015
                32187
                11387036
                1f48bbd6-d4eb-4f31-b609-4ad169fdfa49
                Copyright © 2001 Leemans et al., licensee BioMed Central Ltd
                History
                : 7 February 2001
                : 16 March 2001
                : 16 March 2001
                Categories
                Research

                Genetics
                Genetics

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