The 5th annual Canadian epigenetics meeting hosted by the Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC) took place from Sept 30-Oct 3 2018 at the picturesque Esterel Resort north of Montréal Quebec. Overall, the meeting provides a look at all types of health-focused epigenetics research in Canada, with some speakers and attendees from overseas. The meeting has also become a lively networking event, popular among trainees and PIs. The shear volume of the talks on the BAF complex was BAFfling, but they were all informative: you didn’t want to throw the baby out with the BAF-water… and yes, all these BAF puns make us want to BAF.
Cigall Kadoch (Harvard Medical School, Broad Institute) opened this meeting with a keynote about her work on the BAF complex in cancer. BAF (SWI/SNF) is a chromatin remodelling complex important for early growth and development. It is composed of 10-14 of 29 possible proteins, allowing for hundreds of possible final complexes. She discussed her work on delineating the role of different BAF proteins in human cancers. Among other work, she showed that an SS18-SSX fusion protein displaces normal SS18 in the BAF complex, forming an altered complex variant that lacks the tumour suppressor BAF47 leading to binding and polycomb repression at the Sox2 locus. Many other researchers also talked about their work on the BAF complex throughout the meeting, including Julie Lessard (IRIC – Université de Montréal) and Siyun Linda Wang (UBC) on the role of BAF genes in cancer, Eric Chater-Diehl (SickKids) on neurodevelopmental disorders, and Jamie Kramer (Western) on knockouts of BAF genes in flies. Several talks also covered epigenetics in cancer. Marie Classon described her work to understand founder cell populations that cause relapse after cancer treatments. She found repressive histone marks and closed chromatin in the drug resistant cells. Frédérick Mallette (Université de Montréal) described how KDM4A depletion induced cellular senescence and telomere deficits.
Kenjiro Shirane from Matthew Lorincz’s lab discussed their recently published work on retrotransposons in oocytes which shows how H3K36me3 directs DNA methylation. At the meeting, he presented new, divergent findings in sperm; namely, there was no HeK36me3 in gene bodies and Set2d was not required for DNAm in the male germline. Pam Hoodless (UBC) discussed her work on epigenetic mechanisms regulating enhancer switching during hepatocyte differentiation. She showed HNF1A can establish and maintain active epigenetic modification at enhancers, in part by directly binding DNA in a compact histone. Mike Wilson (SickKids) described his work on comparative genomic methods to identify ancient enhancers which are highly conserved across species and appear to be important in cardiac development.
Josée Dostie (McGill University) provided an excellent overview of chromatin organization, particularly how chromatin is packaged into topologically associating domain (TADs) and 3C technologies to assess these structures. She described her work using these techniques to understand the lncRNA HOTAIRM1 in the regulation of Hox gene expression. Nicole Francis, Marie Kmita, and Tarik Moroy (IRCM) also described work on chromatin structure, including the role of R-loops in PRC2 regulation.
Attendees were also provided an accessible look at some of the computational techniques becoming popular in epigenomics. Anshul Kundaje (Stanford University) provided a clear walkthrough of what a neuronal network is (essentially just layers of pattern detectors). He described his work on DeepLIFT, a tool to compute importance scores in deep neural networks. Understanding transcription factor binding motifs through neural networks can be problematic with traditional neural networks; DeepLIFT decomposes the path of each input neuron to assess how important each nucleotide is in TF binding sites. Michael Hoffman (Princess Margaret Cancer Centre) described an alternate approach for validating induvial ChIP-seq experiments in rare cell populations: to use RNA-seq to learn the association between local TF binding and global cellular states. Theodore Perkins (Ottawa Hospital Research Institute) described RECAP, a tool to find the true significance level of ChIP-seq peaks.
The meeting wrapped up with several talks on neruoepigenetics. Jamie Kramer (Western) knocked out various SWI/SNF genes and observed the effects on brain development and behaviour in files. Annie Vogel (University of British Columbia) described work recently published in preprint from her work in Janine Lasalle’s lab on DNA methylation change at microglia-associated genes in post-mortem ASD brain samples. And we’d be remiss if we didn’t mention the lively poster sessions, which have become somewhat infamous at these CEEHRC meetings: they start at 8pm with the conversation (and the wine) flowing well into the night.
The next CEEHRC meeting will be held Nov 17 – 20, 2019 at The Rimrock Resort, Banff, AB. Epigenie will be there again, and we hope to see many of you.