SPP 1129:  Epigenetics

• Subject Area: Medicine ; Biology
• Term: from 2002 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5471461

• Final Report Year: 2010

Final Report Abstract

In 2002 the priority program SPP1129 „Epigenetics" started with fifteen evaluated projects of which nine were based at university institutes and 6 at non-university research institutions (DKFZ, EMBL, MPI, FG). The programme linked a broad variety of topics focussing on fundamental scientific problems of epigenetic control in three main areas: the basic molecular principles of epigenetic control, the consequence of epiegentic control on developmental processes in model organisms and the principles of epigenetic inheritance in human. On the molecular side several projects aimed at analysing the basic principles of DNA-methylation setting, maintenance and removal, the effects and control of histone modifications on chromatin, the role of non-coding RNAs (RNAi) in targeting epigenetic information and the participation of remodelling complexes in transcriptional control. On the biological side phenomena such as the evolution and functional control of genomic imprinting, the molecular basis for dosage compensation and the developmental control of gene expression were addressed. Over three consecutive rounds of selection the participating projects remained rather constant and developed a strong network with manyfold interactions between participants on all levels. This growing interaction becomes evident through several joined projects, joined publications and novel programme applications emerging from the SPP. There was also strong component to exchange unpublished data (not only at the annual meetings), technologies, protocols and materials. In this respect the „retreat" like atmosphere at annual meetings was very helpful to foster a vivid exchange between PIs, postdocs and PhD students. Through joined conferences with other SPP initiatives (SPP1109 on stem cells) and the BBSRC program on „Epigenetics" and by inviting external guest speakers the programme also promoted novel contacts and created a broad visibility of epigenetics research. On the scientific side the programme were very productive.

Publications

• (2004) Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila. Genes Dev 18: 2973-2983
  Ebert A, Schotte G, Lein S, Kubicek S, Krauss V, Jenuwein T, Reuter G
  
• (2004) The Dnmt1 DNA-(cytosine C5)-methyltransferase methylates DNA processivly with high preference for hemimethylated target sites, J. Biol. Chem. 279, 483S0-9
  Hermann, A., Goyal, R. & Jeltsch, A.
  
• (2005) Chriz, a chromodomain protein specific for the interbands of Drosophila melanogaster. Chromosome 114, 54-66
  Gortchakov, A., Eggert, H., Gan, M., Mattow, J., Zhimulev, I. F., Saumweber, H.
  
• (2005) Chromatin inactivation precedes de novo DNA methylation during the progressive epigenetic silencing of the RASSF1A promoter. Mol Cell Biol. May;25(10):3923-33
  Strunnikova M, Schagdarsurengin U, Kehlen A, Garbe JC, Stampfer MR, Dammann R
  
• (2005). Trapped in action - direct visualization of Dnmt1 activity in living cells. Nature Methods, 2, 751-756
  Schermelleh, L., Spada, F., Easwaran, H. P., Zolghadr, K., Margot, J. B., Cardoso, M. C. and Leonhardt, H.
  
• 2005. Evolution of the Beckwith-Wiedemann syndrome region in vertebrates. Genome Research 15: 146- 153
  Paulsen M, T. Khare, C. Burgard, S. Tierling and J. Walter
  
• Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J Cell Biol. 2005 Jun 6:169(5):733-43
  Brero A, Easwaran HP, Nowak D, Grunewald I, Cremer T, Leonhardt H. Cardoso MC
  
• Microdeletion and IGF2 loss of imprinting in a cascade causing Beckwith-Wiedemann syndrome with Wilms' tumor. Nat Genet.; 37(8):785-6; 2005
  Prawitt D, Enklaar T, Gartner-Rupprecht B, Spangenberg C, Lausch E, Reutzel D, Fees S, Korzon M, Brozek I, Limon J, Housman DE, Pelletier J, Zabel S
  
• (2006) Identification of cis- and trans-acting factors possibly modifying the risk of epimutations on chromosome 15. Eur J Hum Genet 14: 752-758
  Zogel C, Böhringer S, Groß S, Varon R, Suiting K, Horsthemke B
  
• (2006) Nucleoporins are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol Cell 21, 1-13
  Mendjan, S, Taipale, M, Kind, J, Holz, H, Gebhard, P, Schelder, M, Vermeulen, M, Buscaino, A, Duncan, K, Mueller, J, Wilm, M, Stunnenberg, H, Saumweber, H, and Akhtar, A
  
• (2006) Two substrates are better than one: dual specificities for Dnmt2 methyltransferases. Trends in Biochemical Sciences 31, 306-308
  Jeltsch, A., Nellen, W. & Lyko, F.
  
• (2007). Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445,671-675
  Barreto, G., Schäfer, A., Marhold, J., Stach, D., Swaminathan, S.K., Handa, V., Doderiein, G., Maltry, N., Wu, W., Lyko. F., and Niehrs, C.
  
• (2008) A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader-Willi syndrome. Eur J Hum Genet, 18:1439-48
  Kanber D, Giltay J, Wieczorek D, Zogel C, Hochstenbach R, Caliebe A, Kuechler A, Horsthemke B, Suiting B
  
• (2008): Structure and function of Dnmt3a and Dnmt3/3L nucleoprotein filaments. Nucleic Acids Res. 36(21), 6656-6663
  Jurkowska, R.Z., Ragozine,S., Ansbach, N., Urbanke, C, Nellen, W.. Cheng, X. and Jeltsch, A.
  
• Specific interaction of a chromatin remodeling complex with a conserved structure within a small non-coding RNA. EMBO Rep. (2008) 9, 774-780
  Mayer, C., Neubert, M., Grummt, I.
  
• (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
  Phaike S, Nickel O, Walluscheck D, Hortig F, Onorati MC, Reuter G
  
• Essential role of the glycosyltransferase Sxc/Ogt in Polycomb repression. Science 325, 2009, 93-96
  Gambetta, M. C., Oktaba, K. and Müller, J.
  (See online at https://doi.org/10.1126/science.1169727)
• TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of active genes leading to DNA demethylation. Mol. Cell (2009) 33, 344-353
  Schmitz, K. M., Schmitt, N., Hoffmann-Rohrer, U., Schäfer, A., Grummt, I., Mayer, C.
  
• (2010) "DNA demethylation and DNA repair in mouse zygotes". EmbO J. 2010, 29(11): 1877-88
  Wossidio, M., Arand, J., Sebastiane, V., Lepikhov, K., Boiani, M., Reinhardt, H., Scholer, H. and Walter.,J.
  
• Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate. Proc Natl Acad Sci USA. 2010 Mar 23:107(12):5522-7
  Ehrentraut S, Weber JM, Dybowski JN, Hoffmann D, Ehrenhofer-Murray AE