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PMID: 21288872 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of elongator subunit Elp3 in Drosophila melanogaster larval development and immunity.

Genetics ·Vol. 187 ·No. 4 ·2011-04-00 ·Pages 1067-75

Walker J, Kwon SY, Badenhorst P, East P, McNeill H, Svejstrup JQ

Abstract

The Elongator complex has been implicated in several cellular processes, including gene expression and tRNA modification. We investigated the biological importance of the Elp3 gene in Drosophila melanogaster. Deletion of Elp3 results in larval lethality at the pupal stage. During early development, larval growth is dramatically impaired, with progression to the third instar delayed for ∼24 hr, and pupariation occurring only at day 14 after egg laying. Melanotic nodules appear after 4 days. Microarray analysis shows that stress response genes are induced and ecdysone-induced transcription factors are severely repressed in the mutant. Interestingly, the phenotypes of Elp3 flies are similar to those of flies lacking the domino gene, encoding a SWI/SNF-like ATP-dependent chromatin-remodeling enzyme. Indeed, the gene expression profiles of these mutants are also remarkably similar. Together, these data demonstrate that Drosophila Elp3 is essential for viability, normal development, and hematopoiesis and suggest a functional overlap with the chromatin remodeler Domino.

MeSH Terms
Animals Chromatin/genetics,metabolism Chromatin Assembly and Disassembly Drosophila Proteins/genetics Drosophila melanogaster/genetics,growth & development Ecdysone/physiology Gene Deletion Gene Expression Profiling Gene Expression Regulation, Developmental Genes, Lethal Histone Acetyltransferases/genetics,metabolism Larva/genetics,metabolism Linear Models Nerve Tissue Proteins/genetics,metabolism Oligonucleotide Array Sequence Analysis Pupa/metabolism Transcription Factors/genetics,metabolism
Chemicals
Chromatin Drosophila Proteins Nerve Tissue Proteins Transcription Factors Ecdysone ELP3 protein, Drosophila Histone Acetyltransferases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Walker Jane
Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, United Kingdom. [email protected]
Kwon So Yeon
Badenhorst Paul
East Phil
McNeill Helen
Svejstrup Jesper Q
References (56)
56 references, click to expand
  1. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis.
    Development. 1998 May;125(10):1909-20 PMID: 9550723
  2. An iron-sulfur cluster domain in Elp3 important for the structural integrity of elongator.
    J Biol Chem. 2009 Jan 2;284(1):141-149 PMID: 18986986
  3. An early step in wobble uridine tRNA modification requires the Elongator complex.
    RNA. 2005 Apr;11(4):424-36 PMID: 15769872
  4. Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter.
    Cell. 2003 Dec 12;115(6):751-63 PMID: 14675539
  5. The elongata mutants identify a functional Elongator complex in plants with a role in cell proliferation during organ growth.
    Proc Natl Acad Sci U S A. 2005 May 24;102(21):7754-9 PMID: 15894610
  6. Transcriptomic profiles of Drosophila melanogaster third instar larval midgut and responses to oxidative stress.
    Insect Mol Biol. 2008 Aug;17(4):325-39 PMID: 18651915
  7. Yantar, a conserved arginine-rich protein is involved in Drosophila hemocyte development.
    Dev Biol. 2004 Sep 1;273(1):48-62 PMID: 15302597
  8. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
    Development. 1993 Jun;118(2):401-15 PMID: 8223268
  9. Drosophila immunity: analysis of larval hemocytes by P-element-mediated enhancer trap.
    Genetics. 1997 Oct;147(2):623-34 PMID: 9335599
  10. Human Elongator facilitates RNA polymerase II transcription through chromatin.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1241-6 PMID: 11818576
  11. The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity.
    Dev Biol. 2008 Apr 15;316(2):538-47 PMID: 18334252
  12. A multiprotein complex that interacts with RNA polymerase II elongator.
    J Biol Chem. 2001 Aug 10;276(32):29628-31 PMID: 11390369
  13. Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects.
    EMBO J. 1995 Jun 15;14(12):2857-65 PMID: 7796812
  14. Interactions and developmental effects of mutations in the Broad-Complex of Drosophila melanogaster.
    Genetics. 1988 Feb;118(2):247-59 PMID: 3129334
  15. Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration.
    J Cell Biol. 2005 Feb 14;168(4):567-73 PMID: 15699212
  16. A second catalytic domain in the Elp3 histone acetyltransferases: a candidate for histone demethylase activity?
    Trends Biochem Sci. 2002 Mar;27(3):115-7 PMID: 11893502
  17. Characterization of a six-subunit holo-elongator complex required for the regulated expression of a group of genes in Saccharomyces cerevisiae.
    Mol Cell Biol. 2001 Dec;21(23):8203-12 PMID: 11689709
  18. Hemese, a hemocyte-specific transmembrane protein, affects the cellular immune response in Drosophila.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2622-7 PMID: 12598653
  19. Familial dysautonomia is caused by mutations of the IKAP gene.
    Am J Hum Genet. 2001 Mar;68(3):753-8 PMID: 11179021
  20. Transcriptional inhibition of genes with severe histone h3 hypoacetylation in the coding region.
    Mol Cell. 2002 Oct;10(4):925-33 PMID: 12419235
  21. The Drosophila nucleosome remodeling factor NURF is required for Ecdysteroid signaling and metamorphosis.
    Genes Dev. 2005 Nov 1;19(21):2540-5 PMID: 16264191
  22. Histone modifications defining active genes persist after transcriptional and mitotic inactivation.
    EMBO J. 2005 Jan 26;24(2):347-57 PMID: 15616580
  23. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo.
    Mol Cell. 2002 Apr;9(4):799-809 PMID: 11983171
  24. The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine.
    Mol Microbiol. 2006 Feb;59(3):795-806 PMID: 16420352
  25. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme.
    Mol Cell. 1999 Jul;4(1):123-8 PMID: 10445034
  26. Overlapping roles for the histone acetyltransferase activities of SAGA and elongator in vivo.
    EMBO J. 2000 Jun 15;19(12):3060-8 PMID: 10856249
  27. A directed screen for genes involved in Drosophila blood cell activation.
    Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14192-7 PMID: 15381778
  28. Plant Elongator regulates auxin-related genes during RNA polymerase II transcription elongation.
    Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1678-83 PMID: 20080602
  29. Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomia.
    Mol Cell. 2006 May 19;22(4):521-31 PMID: 16713582
  30. Elongator complex: how many roles does it play?
    Curr Opin Cell Biol. 2007 Jun;19(3):331-6 PMID: 17466506
  31. Elongator interactions with nascent mRNA revealed by RNA immunoprecipitation.
    Mol Cell. 2004 May 21;14(4):457-64 PMID: 15149595
  32. The Caenorhabditis elegans Elongator complex regulates neuronal alpha-tubulin acetylation.
    PLoS Genet. 2010 Jan 22;6(1):e1000820 PMID: 20107598
  33. Summaries of Affymetrix GeneChip probe level data.
    Nucleic Acids Res. 2003 Feb 15;31(4):e15 PMID: 12582260
  34. Purification and characterization of the human elongator complex.
    J Biol Chem. 2002 Jan 25;277(4):3047-52 PMID: 11714725
  35. Salty dog, an SLC5 symporter, modulates Drosophila response to salt stress.
    Physiol Genomics. 2009 Mar 3;37(1):1-11 PMID: 19018044
  36. A humoral stress response in Drosophila.
    Curr Biol. 2001 May 1;11(9):714-8 PMID: 11369236
  37. Cloning, characterization, and genomic structure of the mouse Ikbkap gene.
    DNA Cell Biol. 2001 Sep;20(9):579-86 PMID: 11747609
  38. New insights into Drosophila larval haemocyte functions through genome-wide analysis.
    Cell Microbiol. 2005 Mar;7(3):335-50 PMID: 15679837
  39. Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin.
    Cell. 2009 Feb 6;136(3):551-64 PMID: 19185337
  40. The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus.
    Mol Gen Genet. 1993 Apr;238(1-2):33-7 PMID: 8479437
  41. A family of Turandot-related genes in the humoral stress response of Drosophila.
    Biochem Biophys Res Commun. 2001 Jun 22;284(4):998-1003 PMID: 11409894
  42. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration.
    Hum Mol Genet. 2009 Feb 1;18(3):472-81 PMID: 18996918
  43. Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation.
    Mol Cell. 2005 Mar 18;17(6):841-53 PMID: 15780940
  44. A role for the elongator complex in zygotic paternal genome demethylation.
    Nature. 2010 Jan 28;463(7280):554-8 PMID: 20054296
  45. Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo.
    Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3517-22 PMID: 11904415
  46. The Elp2 subunit of elongator and elongating RNA polymerase II holoenzyme is a WD40 repeat protein.
    J Biol Chem. 2000 Apr 28;275(17):12896-9 PMID: 10777588
  47. Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis.
    Mol Cell. 2006 Oct 6;24(1):139-48 PMID: 17018299
  48. Loss of mouse Ikbkap, a subunit of elongator, leads to transcriptional deficits and embryonic lethality that can be rescued by human IKBKAP.
    Mol Cell Biol. 2009 Feb;29(3):736-44 PMID: 19015235
  49. Bioconductor: open software development for computational biology and bioinformatics.
    Genome Biol. 2004;5(10):R80 PMID: 15461798
  50. The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila.
    Genes Cells. 2006 Apr;11(4):397-407 PMID: 16611243
  51. RNA polymerase II elongator holoenzyme is composed of two discrete subcomplexes.
    J Biol Chem. 2001 Aug 31;276(35):32743-9 PMID: 11435442
  52. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation.
    Mol Cell. 1999 Jan;3(1):109-18 PMID: 10024884
  53. The ecdysone-inducible Broad-complex and E74 early genes interact to regulate target gene transcription and Drosophila metamorphosis.
    Genetics. 1995 Nov;141(3):1025-35 PMID: 8582609
  54. Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila.
    Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11427-32 PMID: 11027343
  55. Vectors for the expression of tagged proteins in Drosophila.
    Biotechniques. 2001 Dec;31(6):1280-2, 1284, 1286 PMID: 11768656
  56. Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes.
    Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14337-42 PMID: 9826701
Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
1943-2631
Published
2011-04-00
Epub
2011-00-01
Pages
1067-75
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC3070516
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BB/D522470/1 · United Kingdom
Cancer Research UK · United Kingdom
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