The third EMBO conference on Chromatin and Epigenetics took place on June 1st -5th, 2011 at the EMBL (European Molecular Biology Laboratory) in Heidelberg, Germany. Check out the coverage from our correspondent Julia Arand to see what you missed.
Around 400 scientists listened to 49 talks and discussed 233 posters. The organizers Asifa Akhtar (MPI, Freiburg, Germany), Geneviève Almouzni (Marie-Curie Institute, Paris, France), Ortrun Mittelsten Scheid (GMI, Wien, Austria), Wolf Reik (Babraham Institute, Cambridge, UK) and Eran Segal (Weizmann Institute, Revohot, Israel) worked out a great program, with a multifaceted overview over the latest findings in basic epigenetic research in mammals, plants, invertebrates and yeast. In addition to variation of research objects, there was also great diversity of researchers with regards to age, nationality and experience – a fantastic chance for many young scientists to present their data.
All Around the Double Helix: The EMBO Conference Series on Chromatin and Epigenetics
It was the first time that the meeting was held in the EMBL Advanced Training Centre; the perfect setting for scientists investigating DNA since two helices of aisles wind up and down the building, outside and inside. These ”DNA strands” bring visitors up to the roof of the building from where they have a wonderful view. Changing from one helix to the other is possible by walking along a “base pair” bridge. The posters were displayed along these DNA strands during the whole conference and the attendees could learn about the new achievements in the field of epigenetics whenever they wanted – with ample space for lively discussion and quiet contemplation. A jury had the difficult task of selecting the best two posters out of 233. The exclusion of posters from PIs and posters with data already published in Science, Nature or Cell did not make this duty much easier. However, the two chosen winners gave impressive talks and were rewarded with Kindle eBook readers.
Aside from the fixed program, there was enough time in the breaks, poster sessions, lunches, dinners and beer sessions to talk to other scientists, promoting new and enhancing old collaborations.
Despite strong competition from the coinciding illumination of the famous castle in the city, the traditional party on the last night of the conference with live music was well attended, and the participants enjoyed dancing, drinking and chatting.
Good news also at the end: the organizing committee announced that this might not have been the last EMBO Conference Series on Epigenetics and Chromatin!
Systems View on Genome Function
Joke van Bemmel NKI, Netherlands
By analyzing protein DNA interactions using DamID, they found five distinguishable types of chromatin in Drosophila, each of them having at least two unique interacting proteins.
François Roudier CNRS-IBENS, France
Dr Roudier then made the link to the plant genome, finding four related chromatin types. He finished his talk with the statement that “epigenomes of multicellular eukaryotes have similar and rather simple principles of organization”.
Kristin Brogaard Northwestern University, USA
Dr. Brogaard told us about a new method to localize nucleosomes on the DNA. This method is more accurate than previous methods, since it does not employ micrococcal nuclease treatment, which has a preference for certain sequences. The nucleosome positioning, according to this new method, seems to be sharply defined. There are movements of only about 10 bp observed.
Amos Tanay Weizmann Institute, Israel
Dr Tanay used his in vitro model of cancer development to show that “extensive DNA hypermethylation occurs through a stochastic, parallel and gradual process that is not directly coupled with gene expression or phenotypic selection”. They calculated that about 1 CpG per 500 CpGs and generation gets methylated. Furthermore, they claim not only a loss of CpG positions in the genome, but also a rapid gain of CpGs in specific regions.
Control of Gene Expression: Transcribe or not Transcribe
Fred Berger Temasek Lifesciences Laboratory, Singapore
Dr. Berger focused on imprinting in plants. Here, imprinting can be found in the endosperm after fertilization, due to a DNA demethylation of the central cell genome. So far, imprinting was thought to be only related to CpG context, since both the DNA demethylase DEMETER as well as the transcriptional inactivation of DNA methyltransferase Met1, which is responsible for CpG methylation, are needed for setting up the imprinting. Berger reported now, that also an asymmetry in the RNA dependent DNA methylation (RdDM) is needed for imprinting of several loci. The RdDM pathway is only active in the sperm and not in the central cell, comparable to Met1 expression.
X Inactivation: A Matter of Choice
Joost Gribnau Erasmus MC, Netherlands
Dr. Gribnau is analyzing the initiation of random X-Inactivation. The important question is how are the X-Chromosomes counted? They discovered that the region around Rnf12 is important for counting. By applying an artificial Rnf12 locus in male cells, these show inactivation of the single X-Chromosome. They claim that Rnf12 is acting in trans by activating Xist. Currently, they are looking for interacting partners and found for example Rex1, a zinc finger protein regulated by Oct4 and Nanog.
Maria-Elena Torres-Padilla IGBMC, France
Dr. Torres-Padilla focuses on the transcription and epigenetics of repetitive elements during early mouse development. By comparing the transcription of different types of repetitive elements relative to each other from oocyte to blastocyst, they found an increase in the fraction of transcribed non-LTR-Retrotransposons. However, in total they found a reduction of transcription for all the elements. Furthermore, they looked for histone modifications at the different types of repetitive elements by ChIP. For this analysis, they collected 1200 embryos per experiment! They found that the silencing of the elements correlates only with the loss of active histone modifications. They could not find an increasing amount of repressive histone marks.
Coupling Signaling to Chromatin and Transcription
Jörn Walter Saarland University, Germany
This session was dominated by recently discovered 6th base of the genome – 5-hydroxymethylcytosine (5hmC). Dr. Walter talked about the active DNA demethylation in the zygote. The finding of 5hmC sheds new light on this process. His group showed that Tet3 converts a big part of 5mC in the paternal DNA into 5hmC. Stella/PGC7 protects the DNA in maternal pronucleus from hydroxylation. Furthermore, they found that 5mC to 5hmC conversion in the zygote is conserved amongst the mammals.
Due to the apparent importance of 5hmC in development and growing amount of data showing 5hmC presence in many tissues, the methods for analyzing the location of 5hmC are further evolving.
William Pastor Immune Disease Institute, USA
Dr. Pastor gave insights into the methods developed in their lab. They mapped 5hmC in ESCs by pulling down the derivatives of 5hmC (either using GLIB, adding Biotin labeled glucose group to 5hmC, or by recognition of cytosine 5-methylenesulfonate, the product of 5hmC after bisulfite treatment, by specific antibody). Both approaches give rather similar results. They found 5hmC in ESCs extensively at promoters associated with bivalent histone modification marks (co-localized H3K4me3 and H3K27me3). However, he also mentioned that many of recently published papers describing the mapping of 5hmC contain some discrepancies.
The hope is now that there will be a robust method established to map 5hmC at base pair resolution. One of the techniques exploits the PCR slowdown if 5hmC is present in the DNA template. The Pacific Biosciences sequencer can measure how long does it take for DNA polymerase to incorporate a base. To increase the slowdown effect of 5hmC they enlarged the hydroxygroup by adding a glucose molecule. Although in vivo data is missing, in vitro results look promising.
From Molecular to Nuclear Architecture
Francis Stewart Technical University Dresden
Dr. Stewart gave insights into functions of the six mammalian H3K4 methyltransferases. H3K4me is associated with active chromatin. In KO experiments in mice they found that all H3K4 methyltransferases are required for proper development, each having specialized tasks. However, not all promoters that loose H3K4 methylation show a change in their expression levels.
Jacqueline Mermoud Babraham Institute, UK
In contrast, Dr. Mermoud is interested in histone modifications associated with silent chromatin and tries to elucidate how the maintenance of silent chromatin in mammals works. They found SMARCAD1, an ATP dependent chromatin-remodeler, to be responsible for the maintenance of histone modifications, which are associated with transcriptionally silent chromatin. Knocking out SMARCAD1 they observed an increase in histone acetylation and reduction of H3K4 methylation and HP1 binding. Furthermore, they report that SMARCAD1 is associated with transcriptional repressors like KAP1, histone deacetylases and the histone methyltransferase G9a. Interestingly, they found SMARCAD1 directly interacting with PCNA, a component in the replication machinery, and co-localized at replication sites.
Genome Stability and Dynamics
Primo Schär University of Basel, Switzerland
Dr. Schär showed us the link between Epigenetics and DNA repair. Knocking out the DNA glycosylase TDG they found a DNA hypermethylation of the genome, suggesting that TDG is needed to avoid or repair undesired DNA methylation events. They found binding of TDG at CpG rich regions. However, by knocking out TDG they observed more methylation differences in CpG poor regions. So, there must be two different mechanisms how TDG is recruited and working. Furthermore, they found changes in histone modification. Therefore, DNA repair events and maintaining the epigenome are closely related mechanisms.
Craig Pikaard Indiana University, USA
Dr. Pikaard could show convincingly in elegant assays that the two plant-specific RNA polymerases IV and V, which have non-redundant functions in siRNA-mediated DNA methylation and silencing, have indeed polymerase activity. He further demonstrated that Pol IV works hand in hand with the RNA-dependent RNA polymerase, the two together producing those double stranded RNAs that are the substrates for small RNA production.
The Plenary Lecture
Peer Bork EMBL, Heidelberg
On the last night, shortly before the banquet and the party, Dr. Bork gave the plenary lecture. He presented a “cute small and manageable in vivo model system, which can cheaply be studied” – the bacteria. Analyzing the DNA in the gut of humans, his group could identify more than 4,000,000 bacterial genes. Analogous to blood group differences, humans can be categorized into three distinct types, according to the bacteria living in their guts. The epigeneticists seemed to enjoy taking a glimpse into a different discipline and to hear about a story that made it even into many popular newspapers.
**EpiGenie would like to thank Julia Arand, Dipl. Biol., who is in the Dept. of Genetics/Epigenetics at Saarland University in Germany for providing coverage of this conference.