** Thanks to Alison Hirukawa, a talented graduate student at McGill University in Canada, for covering this great event for us.
‘Epigenomics in Development and Disease’, the 3rd edition of the Canadian Conference in Epigenomics, was held in picturesque Estérel, Quebec, Canada, from September 18th-21st. The size and atmosphere of the conference facilitated a tremendous amount of interaction between trainees and senior PIs, and plenty of opportunities to network with distinguished speakers from the fields of epigenomics and chromatin biology. Presenters shared a great deal of exciting unpublished work (not covered in this report, sorry) and there was plenty of discussion during post-talk Q&A sessions, making it a truly engaging event.
Measuring Patterns within the Nucleosomal Unit with Internal-Standard Calibrated ChIP (ICeChIP)
Alex Ruthenberg | University of Chicago, Chicago, Illinois, USA
The opening session of the conference included an interesting presentation, followed by a spirited discussion on ChIP-Seq. While ChIP-Seq is an essential technique in the field of epigenetics, it is difficult to reproduce or draw comparisons across experiments, due to a multitude of factors including lot variability between polyclonal antibodies. To address this, Alex Ruthenberg’s group devised ICeChIP (Internal Standard Calibrated ChIP).
ICeChIP involves spiking a native chromatin sample with barcoded nucleosomes prior to the immunoprecipitation, allowing for an internal standard to reveal the average amount of a given histone modification at a locus. For those interested in the technology, the semisynthetic nucleosome spiking control utilized for ICeChIP will be commercially available as part of a kit produced by Epicypher in the near future.
MLL in the Control of Cell Identity and Disease
Yali Dou | University of Michigan, Ann Arbor, Michigan, USA
Yali Dou presented an elegant story outlining how inhibition of Mll1, the histone methyltransferase that facilitates H3K4me3, can reprogram mouse epiblast cells to a naive Embryonic Stem (ES) cell state. While previous work concerning de-differentiation has involved manipulating master transcription factors that govern ‘stemness’ and was relatively inefficient, the Dou group found that a transient pharmacological block of Mll1 (MM-401) was sufficient to induce a stable transcriptional change in epiblast cells, reprogramming them to a fully pluripotent state.
Mapping Regulatory Elements Using ATAC-Seq in Stimulated Immune Cells
Daniel Gaffney | Welcome Trust Sanger Institute, Cambridge, UK
Daniel Gaffney’s group is interested in combing statistical methods with epigenomics to better understand how cellular and molecular consequences of changes in gene regulatory regions. Recent work as has involved the integration of a statistical approach (RASQUAL) with QTL mapping and open chromatin conformation mapping (via ATAC-Seq) to improve fine mapping of regulatory variants.
Termed chromatin accessibility QTL (caQTL), the group has recently published the first map of caQTL in a European population. Given the tendency to focus on tissue rather than a stimulated state and since disease situations can be hidden in temporal states, future work from the group will employ an iPS cells (induced pluripotency stem). In this model iPS cells will differentiated towards a macrophage lineage, allowing for the mapping the expression QTL at chromatin the naïve state and various differentiated states.
DNA Methylation: Biomarker and Therapeutic Target in Cancer
Daniel de Carvalho | University of Toronto, Toronto, Canada
Daniel de Carvalho presented an excellent example of how scientific discoveries from the bench can be rapidly translated to the clinic. While DNA demethylating agents have been approved for certain malignancies, their mechanism of action was unclear. The de Carvalho group recently found that these agents activate toxic cellular anti viral programs in colectoral tumour cells through transcriptional activation of endogenous retroviral sequences.
Termed ‘viral mimicry’, they found that low doses of a DNA demthylating agent induced dsRNS and IRF7 activation. Interestingly, IRF7 levels have been positively correlated with CD8+ effector T cells, opening up the possibility of combinatorial therapy. To this end, in collaboration with Dr. Lillian Su at the Princess Margaret Cancer Center, the METADUR study has been launched, in which patients with advanced solid tumors will receive azacitidine and checkpoint inhibitor anti-PDL1.
Other highlights from the conference included a talk from Dr. Cheryl Arrowsmith, from the University of Toronto affiliated Structural Genomics Consortium (SGC). The mandate of the SGC is to accelerate research by making all of its output available to the scientific community, and in this spirit the SGC has made a wide variety of epigenetic inhibitors available to researchers, at no cost. http://www.thesgc.org/reagents-resources
The conference also hosted a series of workshops on epigenomics for the less computationally inclined participants. David Bujold from Genome Quebec, led an informative session on publicly available data sets (such as a the IHEC data portal http://epigenomesportal.ca/ihec/). Canadian readers might be interested to learn that it is possible to access GenAP with a Compute Canada account (it’s all free!) GenAP is a computing platform for life science researches that allows you to run programs such as the Galaxy Web application and various bioinformatics data analysis pipelines. https://genap.ca/public/home
Overall the meeting was a great mix of bioinformaticians, clinicians and wet lab researchers. It’s exciting to hear that the conference will become an annual event and would be highly recommend it to anyone working in the field of epigenetics.