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  • 1
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    Systematic genetic analysis of muscle morphogenesis and function in Drosophila (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-03-12
    Description: Systematic genetic approaches have provided deep insight into the molecular and cellular mechanisms that operate in simple unicellular organisms. For multicellular organisms, however, the pleiotropy of gene function has largely restricted such approaches to the study of early embryogenesis. With the availability of genome-wide transgenic RNA interference (RNAi) libraries in Drosophila, it is now possible to perform a systematic genetic dissection of any cell or tissue type at any stage of the lifespan. Here we apply these methods to define the genetic basis for formation and function of the Drosophila muscle. We identify a role in muscle for 2,785 genes, many of which we assign to specific functions in the organization of muscles, myofibrils or sarcomeres. Many of these genes are phylogenetically conserved, including genes implicated in mammalian sarcomere organization and human muscle diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnorrer, Frank -- Schonbauer, Cornelia -- Langer, Christoph C H -- Dietzl, Georg -- Novatchkova, Maria -- Schernhuber, Katharina -- Fellner, Michaela -- Azaryan, Anna -- Radolf, Martin -- Stark, Alexander -- Keleman, Krystyna -- Dickson, Barry J -- England -- Nature. 2010 Mar 11;464(7286):287-91. doi: 10.1038/nature08799.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. schnorrer@biochem.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computational Biology ; Drosophila melanogaster/*embryology ; Genes, Insect/*genetics ; Genome-Wide Association Study ; Genomic Library ; Larva ; Male ; Muscles/embryology ; RNA Interference
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Genome-scale functional characterization of Drosophila developmental enhancers in vivo (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-06-05
    Description: Transcriptional enhancers are crucial regulators of gene expression and animal development and the characterization of their genomic organization, spatiotemporal activities and sequence properties is a key goal in modern biology. Here we characterize the in vivo activity of 7,705 Drosophila melanogaster enhancer candidates covering 13.5% of the non-coding non-repetitive genome throughout embryogenesis. 3,557 (46%) candidates are active, suggesting a high density with 50,000 to 100,000 developmental enhancers genome-wide. The vast majority of enhancers display specific spatial patterns that are highly dynamic during development. Most appear to regulate their neighbouring genes, suggesting that the cis-regulatory genome is organized locally into domains, which are supported by chromosomal domains, insulator binding and genome evolution. However, 12 to 21 per cent of enhancers appear to skip non-expressed neighbours and regulate a more distal gene. Finally, we computationally identify cis-regulatory motifs that are predictive and required for enhancer activity, as we validate experimentally. This work provides global insights into the organization of an animal regulatory genome and the make-up of enhancer sequences and confirms and generalizes principles from previous studies. All enhancer patterns are annotated manually with a controlled vocabulary and all results are available through a web interface (http://enhancers.starklab.org), including the raw images of all microscopy slides for manual inspection at arbitrary zoom levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kvon, Evgeny Z -- Kazmar, Tomas -- Stampfel, Gerald -- Yanez-Cuna, J Omar -- Pagani, Michaela -- Schernhuber, Katharina -- Dickson, Barry J -- Stark, Alexander -- England -- Nature. 2014 Aug 7;512(7512):91-5. doi: 10.1038/nature13395. Epub 2014 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2] Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA (B.J.D.); Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA (E.Z.K.). ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria. ; 1] Research Institute of Molecular Pathology (IMP), Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila melanogaster/*embryology/*genetics ; Embryonic Development/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genome, Insect/*genetics ; Internet ; Nucleotide Motifs/genetics ; Organ Specificity/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; User-Computer Interface
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-12-18
    Description: Gene transcription in animals involves the assembly of RNA polymerase II at core promoters and its cell-type-specific activation by enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has been less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different core promoters might exhibit an intrinsic specificity to certain enhancers. This is conceivable, as various core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly found at either developmentally regulated or at housekeeping genes. Here we show that thousands of enhancers in Drosophila melanogaster S2 and ovarian somatic cells (OSCs) exhibit a marked specificity to one of two core promoters--one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor--and confirm the existence of these two classes for five additional core promoters from genes with diverse functions. Housekeeping enhancers are active across the two cell types, while developmental enhancers exhibit strong cell-type specificity. Both enhancer classes differ in their genomic distribution, the functions of neighbouring genes, and the core promoter elements of these neighbouring genes. In addition, we identify two transcription factors--Dref and Trl--that bind and activate housekeeping versus developmental enhancers, respectively. Our results provide evidence for a sequence-encoded enhancer-core-promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zabidi, Muhammad A -- Arnold, Cosmas D -- Schernhuber, Katharina -- Pagani, Michaela -- Rath, Martina -- Frank, Olga -- Stark, Alexander -- England -- Nature. 2015 Feb 26;518(7540):556-9. doi: 10.1038/nature13994. Epub 2014 Dec 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Dr Bohr-Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517091" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; DNA-Binding Proteins/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*embryology/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genes, Essential/*genetics ; Genome, Insect/genetics ; Models, Genetic ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; Substrate Specificity/genetics ; Transcription Factors/metabolism ; Transcriptional Activation/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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