We unfortunately couldn’t make the 3rd International Conference on Epigenetics in Australia, but lucky for us researchers Nick Wong and Boris Novakovic were cool enough to provide us with some of the great highlights. The conference was held in Melbourne at The Sebel overlooking the Formula One racetrack and Albert Park Lake.
It was an exciting meeting with over 260 delegates of mainly Australian epigenetic researchers but with a good mix of international speakers and students as well. Topics covered by this meeting included the role of epigenetics in cancer, the environment, disease development and the cutting edge technologies researchers use to study epigenetic modifications. Imprinting and non-coding RNA was also covered.
The meeting consisted of a stellar cast of both international and local epigenetics researchers including:
- Moshe Syzf (McGill University, Canada),
- Jingde Zhu (Shanghai Cancer Institute, China)
- Art Petronis (University of Toronto, Canada)
- Peter Jones (USC/Norris Comprehensive Cancer Center, USA)
- Wendy Bickmore (Medical Research Council, UK) and
- Benjamin Tycko (Columbia University, USA)
- Susan Clark (Garvan Institute, Sydney)
- Jean Finnegan (CSIRO Plant Industry, Canberra)
- David Tremethick (John Curtain School of Medical Research, Canberra)
- John Mattick (Institute for Molecular Bioscience, Queensland) and
- Marylin Renfree (The University of Melbourne, Melbourne)
Entwined with these talks were presentations from young Australian investigators that were either PhD students or post-docs working on epigenetics.
Moshe Syzf (McGill University, Canada)
Moshe Szyf gave an excellent public lecture as well as the opening plenary lecture overviewing his work with Micheal Meany on the effects of maternal grooming and care on the epigenetic profile of the offspring and demonstrated in animal models at least, that offspring from high licking mothers were less stressed and had a different epigenetic profile than offspring from low licking mothers.
Syzf went on to look in humans to find a similar observation where individuals who were depressed, had a different DNA methylation pattern to those who were not. This was also confirmed in a non-human primate model. Syzf finished by describing how the epigenome (DNA methylation) could be changed through the social and physical environment. “The epigenome changes as a direct response to the social and physical environment and this explains disease pathogenesis”.
Furthermore, Syzf believes it is possible to measure DNA methylation changes in surrogate tissue (blood for schizophrenia research for example), he believes there are systemic changes to DNA methylation across the whole genome that do not necessarily have to be the same changes as those in the diseased tissue. Nevertheless, it is still a worthwhile effort to profile DNA methylation.
Susan Clark (Garvan Institute, Sydney)
Susan Clark described further characterisations of the long range epigenetic silencing she has already published on at 2q14.2 in colorectal cancer samples. Using tiling arrays and next-generation sequencing her group was able to characterise another region at 7p31 that was susceptible to long range epigenetic silencing. This was an uncanny example of the phenomenon Moshe Syzf was describing, a global epigenomic response to the environment in this case transformation towards prostate cancer. What the sequence properties are for permissive long range epigenetic silencing is still unknown and this would be the scope of future work, watch this space.
Art Petronis (University of Toronto, Canada)
Art Petronis argued that we humans are all genetically very similar, but epigenetically very different. By interrogating the unmethylated fraction of genomic DNA from post mortem brains of psychiatric patients, his group found DNA methylation differences at genes associated with brain development including glutamatergic and GABAergic transmission.
Petronis went on to describe twins and speculated that although monozygotic twins can have some epigenetic differences between sibs, dizygotic twins have genetic differences in epigenetics or in another word the zygotes from which the dizygous sibs were derived from are epigenetically different to start with.
Petronis finished his talk by saying epigenetics is important in disease aetiology and demonstrated this with a PubMed survey of epigenetics and disease. He showed that between 2004 and 2009 there was a 118-fold increase in the number of publications describing epigenetic changes associated with disease while genetics and disease only saw a 1.8 –fold increase.
Peter Jones (USC/Norris Comprehensive Cancer Center, USA)
Peter Jones described some new work from his lab and stated that the nucleosome is the epicentre of epigenetics. The nucleosome is where all the action is and it is the histone tail modifications that mediate whether a gene is transcribed or not. With some very elegant molecular techniques he was able to show nucleosome shifting across the transcription start site of GRP78.
By methylating the chromatin DNA using SssI methylase followed by bisulphite conversion, PCR and sequencing, Jones and his team were able to characterise the footprint of nucleosome binding to the DNA. Nucleosome-bound DNA was not methylated by SssI while the linker DNA was. Jones demonstrated that gene regulation was mediated by nucleosome sliding across the transcriptional start site and with the development of a GpC methylase, it is now possible to explore into more depth the role of nucleosome positioning using this technique.
Peter Jones talk was a great segway to Wendy Bickmore’s presentation on higher-order chromosome structure.
Wendy Bickmore (Medical Research Council, UK)
It is still unclear beyond the 30nm fibre how chromatin is further packaged in the nucleus. Bickmore overviewed the role of PRC1 complex in mouse ES-cell differentiation and went further to describe the role of this complex in chromatin compaction. Bickmore showed very elegantly with a simple experiment the requirement of PRC1 in compaction by using a Fluorescence in-situ Hybridisation (FISH) assay looking at two genes within the HOX cluster with a known genomic distance and physical measurement of spatial distance.
The PRC1 mutant was unable to induce differentiation and revealed that the H3K27 methylation mark alone was not sufficient to compact chromatin. Bickmore finished by speculating that PRC1 could be mediating the long-range epigenetic silencing phenomenon (LRES) described in cancer and was starting to look at this in her laboratory. Watch this space.
Benjamin Tycko (Columbia University, USA)
Benjamin Tycko presented a novel method for elucidating CNVs, SNPs and both allele-specific and cis-acting methylation data, called ‘methylation-sensitive SNP array analysis (MSNP). This method has the potential to expand on results from genome-wide association studies (GWAS). He pointed out that 90% of SNPs identified by GWAS are in non-coding regions, so determining whether they are biologically important is hard. Benjamin believes that by using MSNP, DNA methylation can be linked to a particular SNP, and then that DNA methylaton pattern can be analysed over a larger area, potentially linking it to a gene promoter and expression. By doing so, then it is possible in the future to just look at the SNP and predict gene expression.
Benjamin also presented results from a genome-wide DNA methylation analysis of Down syndrome (DS) individuals. His groups showed that DS individuals can be distinguished from control individuals based solely on their methylation profile. Most of the differential methylation is not occurring on chromosome 21, suggesting that there is a systematic epigenetic response to the extra chromosome 21. The presence of these methylation changes in multiple blood cell lineages suggests that the changes are occurring early in development, potentially in the stem cells. Benjamin’s talk transitioned from a technical description of MSNP, to an example of the usefulness of this method in genome-wide DNA methylation analysis in DS.
Australian Scientific Conference-Epigenetics Summary
The Australian Epigenetics conference was a great meeting and it was amazing to see common themes and links coming out from most talks. We didn’t even cover poster presentations, which were just as interesting, and a shining example of the thriving community of epigeneticists in Australia.
– Kindly Provided by conference attendees Nick Wong and Boris Novakovic
Check out the new Australian Epigenetic Alliance Website and keep up to speed on the epigenetics action down under.