Initiation and epigenetic stability of gene silencing in Drosophila
Zusammenfassung der Projektergebnisse
In our work, using the Drosophila model system, we combined systematic genetic analysis of epigenetic processes with biochemical and immunocytological techniques. Mutant isolation and characterization identified new epigenetic functions and allowed their functional dissection in vivo. The studies resolved new insights into early embryonic differentiation of chromatin states and their stable maintenance throughout development. This work finally led to the establishment of a series of high-throughput techniques for systematic molecular cloning of the whole Su(var) gene complement of Drosophila. Based on establishment of a new P element collection tagging genomic sites subjected to gene silencing new molecular processes controlling gene silencing could be resolved. The studies resulted in identification of alternative molecular pathways controlling in Drosophila gene silencing also including DNA methylation dependent processes. Special focus of our studies was directed on clarifying the role of the only putative Drosophila DNA methyltransferase DNMT2 in DNA methylation and gene silencing. Another rather ambiguous project initiated within the SPP consisted in successful establishment of a new monitoring system of gene silencing in germ line cells. With its help it became possible to analysis molecular processes controlling chromatin differentiation in germ line cells and to test for stable transmission of epigenetic states within the germ line linage of Drosophila.
Projektbezogene Publikationen (Auswahl)
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(2003) Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Sem. in Cell and Dev. Biol. 14: 67-75
Schotta G, Ebert A, Dorn R, Reuter G
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(2003) SU(VAR)3-9 a conserved key function in heterochromatic gene silencing. Genetica 117: 149-158
Schotta G, Ebert A, Reuter G
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(2004) Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila. Genes Dev 18: 2973-2983
Ebert A, Schotta G, Lein S, Kubicek S, Krauss V, Jenuwein T, Reuter G
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A silencing pathway to induce H3-K9 and H4-K20 tri-methylation at constitutive heterochromatin. Genes Dev 18: 1251-1262
Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T
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(2005) STD-measurements with SU(VAR)3-9 and S-adenosyl-L-methionine. Biochemistry 44: 6208-6213
Seeger K, Lein S, Reuter G, Berger S
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(2006) Heterochromatic proteins HP1, SU(VAR)3-9 and SUUR are distributed differently in chromosomes of germ-line and somatic cells of Drosophila melanogaster. Chromosoma 115: 296-310
Koryakov DE, Reuter G, Patrizio D, Zhimuliev I
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(2006) Histone modification and the control of heterochromatic gene silencing in Drosophila. Chromosome Research 14: 377-392
Ebert A, Lein S, Schotta G, Reuter G
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(2006) Position effect variegation in Drosophila: A tool to investigate heterochromatin formation. In: Epigenefics, Ed. C D. Allis, T. Jenuwein and D. Reinberg, Cold Spring Harbor Laboratory Press
Elgin SCR, Reuter G
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(2007). Heterochromatin formation in Drosophila is 73 initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3. Mol. Cell 26: 103-115
Rudolph T, Yonezawa M, Lein S, Heidrich K, Kubicek S, Schäfer C. Phaike S, Walther M, Schmidt A, Jenuwein T, Reuter G
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(2008) Human DNMT2 methylates tRNAAsp molecules using a DNA-methyltransferase like catalytic mechanism. RNA 14: 1663-1670
Jurkowski TP, Meusburger M, Phalke S, Maximov V, Helm M, Nellen W, Reuter G, Jeltsch A
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(2009) Cellular mechanism for targeting heterochromatin formation in Drosophila. Int. Rev. Cell. Mol. BioL 273: 1-47
Eissenberg JC, Reuter G
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(2009) Coordinated demethylation and methylation of histones controls heterochromatin formation and gene silencing in Drosophila. Review, in: Chromosomes to Genome, IK International Publishing House Pvt. Ltd., New Delhi, pp. 41-59
Reuter G, Lein S
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(2009) Epigenetic control of retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine 5 methyltransferase DNMT2. Nature Genet. 41: 696-702
Phalke S, Nickel O, Walluscheck D, Hortig F, Onorati MC, Reuter G
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(2009) Epigenetics and the control of multicellularity: Chromatin at the nexus of cell division and differentiation. EMBO Rep. 10: 25-29
Reuter G, Cavalli G
