This year’s EMBO Conference on Chromatin and Epigenetics (May 13-17, 2009) took place in the city of the oldest university in Germany (Heidelberg) a bit outside of the city center at the European Molecular Biology Laboratory (EMBL). The conference was dedicated to Alan Wolffe (1959-2001), a major proponent for the idea that chromatin plays a dynamic role in regulating gene expression. The organizers of this year’s conference (Asifa Akhtar, Geneviève Almoouzni, Vincent Colot, Wolf Reik) compiled a marvelous scientific program covering a wide range of burning questions in epigenetics.
The conference started off with a very interesting session on chromatin and non-coding RNAs with a major focus on imprinting, reprogramming and epigenetic balancing. In addition, chromatin dynamics and transcription, as well as whole genome studies were discussed. Besides the very well known players like methylation, acetylation, and phosphorylation, also data on sumoylation, ubiquitination, ADP-ribosylation, and GlcNAc-modification were presented. The meeting closed with a session on epigenetic decisions in development.
What is almost as important as the science behind is time for socializing, meeting colleagues, collaborators and – not to forget – competitors. Even though the scientific schedule was quite dense, there was enough time to discuss at the coffee breaks or the daily beer sessions. Those participants who didn’t find time to meet their target person during beer sessions had another chance at the banquet dinner including its legendary party in the EMBL canteen.
The Epigenome and Small RNA Repertoire in Mammalian Germ Cells
Hiroyuki Sasaki, National Institute of Genetics, Japan
Hiroyuki Sasaki talked about his recent work in mammalian germ cells linking epigenetic events and genomic imprinting. While it is well known that during gametogenesis de novo DNA methyltransferases play a major role for gamete-specific differential methylation, the pathway how the complex is guided to the target remains unsolved.Hiroyuki Sasaki suggested a link between piRNAs and de novo methylation in genomic imprinting. His lab compared deep sequencing data from male and female germ cells and mapped non-repeat small RNAs to imprinted DMRs (DNA methylated regions). On the one hand only a small number of small RNAs at imprinted loci could be identified, on the other hand his group could identify a dependence of an imprinted locus on one of the piRNA complexes (mili) in mouse.
Chromatin Modifications Differentiate Imprinted Genes and Tissue-Specific Silenced Genes
Denise Barlow, CeMM Center for Molecular Medicine of the Austrian Academy of Sciences
Genomic imprinting is not only limited to DNA methylation and small RNAs. Denise Barlow presented what is new in the “Air”. On the maternal allele DNA methylation silences Airn macro non-coding RNAs and Igf2r is active, whereas on the paternal allele the Airn transcript silences the overlapping Igf2r gene. By analyzing chromatin modifications they could show a negative correlation between H3K27me3 and transcription for silent, non-transcribed genes (Pauler et al., Genome Res. 2009), whereas silent imprinted alleles were lacking such a modification. Why do imprinted genes (like male Igf2r) lack H3K27me3? The simple answer is: “The paternal Igf2r promoter is not silenced!” (Latos et al., Development, 2009). The imprinted expression of the Igf2r gene arises by preventing the paternal upregulation, and only the maternal gene is highly expressed during development.
Specialized Transcriptional Machinery Required for RNA-directed DNA Methylation
Marjori Matzke, Gregor Mendel Institute of Molecular Plant Biology, Austria
Let’s switch from mammals to plants and their complex and sophisticated transcriptional machinery. Marjori Matzketalked about new exciting factors involved in RNA-directed DNA methylation (RdDM) where small RNAs are guiding epigenetic proteins to target sites for DNA methylation. The functions of RdDM are not yet understood but roles in development, transposon silencing and stress adaptation have been proposed by several research groups. In addition to the very well known RNA Polymerases I to III, there are two plant-specific RNA polymerases (PolIV and PolV) required for RdDM. To identify new factors involved in the RdDM process her group is applying an efficient forward mutant screen.
They identified nine dms (defective in meristem silencing) mutants, including the previously identified SNF2-like factor DRD1 and two PolV subunits. In a recent publication (Kanno et al., 2008) they describe another factor (an unusual structural maintenance of chromosome (SMC) hinge domain-containing protein) involved in RdDM, functioning via a possible physical link between small RNAs and DNA. Another exciting factor DMS4 (a conserved putative transcription factor) could function either together with PolII in development or with PolV in RdDM.
Marjori finished her talk by saying “Plants have expanded and diversified their transcriptional machinery to include factors dedicated to RNA-mediated, chromatin based silencing.” And we can be sure to hear much more about factors involved in silencing in plants as they have numerous more mutants in their pipeline.
Heterochromatin Reprogramming by RNAi During Cell Division and Differentiation
Robert Martienssen, Gulbenkian Institute, Portugal
“Heterochromatin is transcribed” – but why would you transcribe something what is silenced? This paradox was explained by Rob Martienssen. In plants small RNAs map very closely to heterochromatin. In addition, siRNAs corresponding to transposable elements depend on DNA methyltransferases (MET1) and chromatin remodelers (DDM1) (Lippman et al., Nature 2004). These two genes are required for silencing transposons in the absence of siRNA, as ddm1 mutations are able to make heterochromatic regions euchromatic. They have found that transposons are expressed in pollen. “Why would you express transposons in the germ line?” The explanation: Transposons are only expressed in vegetative nuclei and not in sperm cells, and DDM1 is only expressed in sperm cells but not in vegetative pollen nuclei. And now the final clue! Those small RNAs are mobile and are transported from vegetative nucleus to the sperm cell to keep transposons silent with the help of DDM1 (Slotkin et al., Cell, 2009). The question whether this epigenetic inheritance during replication is conserved between species, still needs to be resolved.
With the talks presented at the conference the latest advances in epigenetics and chromatin were very well covered, and also new directions for epigenetic research away from the epigenetic meaning of imprinting towards the behavioral aspect of imprinting (as put forward by Konrad Lorenz in the last century) were suggested.
Let’s stay tuned and be curious how the field will develop until the next EMBO conference on Chromatin and Epigenetics.
EpiGenie would like to thank Andrea Forster, a PhD student at the Gregor Mendel Institute of Molecular Plant Biology, for covering this great conference for us. Be on the lookout for more complimentary conference registrations from EpiGenie in the near future. Well, they’re not quite complimentary since you have to take notes, but you’d be doing that anyways right?