Latest AEpiA news
Our flagship scientific meeting was held last October – November in Brisbane, where we enjoyed three days of seminars, posters and lively discussion. It was wonderful to see first hand much of the epigenetics research that’s happening in Australia and overseas.
We are very grateful to our international visitors – in particular, keynote speakers Prof Peter Jones from the Van Andel Research Institute, Prof Stephen Baylin from John Hopkins University, and Dr Gavin Kelsey from the Babraham Institute – for travelling to Australia to present some of their latest findings and share many words of wisdom!
We were genuinely impressed by the quality and innovation of the research presented at the meeting – from young students to experienced senior researchers.
We extend warm congratulations to our award winners. We were delighted to present the Young Investigator Award to Qian Du, from Sydney’s Garvan Institute of Medical research, who presented her research on DNA replication timing and the cancer epigenome. Congratulations also to all the Poster Award winners.
Well done to Jason Lee, Vicki Whitehall, Eva Baxter, Darren Korbie and all of the organising committee for a succesful meeting!
Please enjoy the above slideshow of photos from the meeting, and we hope to see you in Western Australia for Epigenetics 2019 – watch this space!
Epigentics 2017 award winners:
Young Investigators Award winner:
Poster Award winners:
Thanks to our sponsors:
Thanks to our journal partner:
Here are some brief highlights of Australian epigenetics publications from the end of last year (2017):
Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function
In this study, Professor Turner and colleagues from Monash University and the Doherty Institute at the University of Melbourne have mapped the dynamic regulation of transcriptional enhancers (TEs) in T cells responding to an acute influenza A infection. By doing so they have identified key epigenetic mechanisms that underpin infection specific T cell differentiation, an essential requirement for pathogen clearance. In their publication in Cell Reports the authors used ChIP-seq to map the histone dynamics of 25,000 putative CD8+ T cell transcriptional enhancers differentially utilized during virus-specific T cell differentiation. The study revealed the acquisition of a non-canonical (H3K4me3+) chromatin signature on a subset of dynamically regulated transcriptional enhancers unique to virus-specific CD8+ T cell differentiation. This identified “the genomic location for T cell lineage-specific transcription factor binding required for virus-specific T cell differentiation” and adds vital pieces to the puzzle of infection specific T cell regulation.
For full text by Russ et al., see – http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31779-5
The DNA Methylation Landscape of CD4þ T cells in Oligoarticular Juvenile Idiopathic Arthritis
From Murdoch Children’s Research Institute and the University of Melbourne, Professor Ellis and colleagues report “a lesser relevance of DNA methylation levels in childhood, compared to adult, rheumatic disease”. In their study, published in the Journal of Autoimmunity, the authors used Illumina HumanMethylation450 arrays to perform a genome-scale analysis of CD4. T cell DNA methylation of oligoarticular juvenile idiopathic arthritis patients and age and sex-matched controls. While adult autoimmune rheumatic diseases, such as rheumatoid arthritis, have been associated with altered DNA methylation, the article reveals that the pediatric autoimmune disease, oligoarticular juvenile idiopathic arthritis, does not show substantially altered methylation in oJIA in CD4. T cells.
For full text by Chavez-Valencia et al., see – https://www.sciencedirect.com/science/article/pii/S0896841117305863
Isogenic Mice Exhibit Sexually-Dimorphic DNA Methylation Patterns Across Multiple Tissues
In this study published in BMC Genomics, A/Professor Suter and colleagues from Sydney’s Victor Chang Cardiac Research Institute aimed to understand the extent to which epigenetic states are influenced by sex; given sexual dimorphism is relevant to so many diseases. For this, the authors used DNA methylation patterns from multiple tissues of isogenic male and female mice. Using this model the authors were able to identify “thousands of sexually dimorphic loci”, which they report to be “largely autonomous to each tissue”. The paper reveals that sex influences methylation patterns in a tissue-specific manner and therefore suggests that at least some of the phenotypes that carry gender bias are derived from gender differences in underlying epigenetic states.
For full text by McCormick et al., see – https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-4350-x
Multiple Innovations in Genetic and Epigenetic Mechanisms Cooperate to Underpin Human Brain Evolution
In their Perspective, Dr Guy Barry and Mainá Bitar explore how the human brain differs from those of other species, with a focus on evolutionary adaptations and functionality. Given only 1% of the human genome is unique compared to a chimpanzee, the authors from Brisbane’s QIMR Berghofer Medical Research Institute have collated a wide range of literature on a range of evolutionary adaptations. The review looks at how “Retooling the Protein Toolbox, Innovations in Regulatory RNA, Alterations to the Basic Genetic Code” and “Epigenetics: Fuelling Brain Plasticity and Adaptive Change” explains how our uniquely evolved human brain has come to be. Interestingly for this epigenetics focused audience, the authors site that an estimated 42% of human-chimpanzee gene expression differences are accounted for by epigenetic differences. The review combines “newly discovered genetic and epigenetic mechanisms with more established concepts” to create a more comprehensive picture of this fascinating field.
For full text by Bitar and Barry see – https://academic.oup.com/mbe/article/35/2/263/4644722?searchresult=1
In a review that discusses the contribution of several cell death pathways to the life and death of activated T cells Zhan et al., highlight a mechanism of epigenetic regulation of cell survival unique to activated T cells. The review by Professor Lew and colleagues from the Walter and Eliza Hall Institute of Medical Research and University of Melbourne the collates the efforts made by studies aimed at understanding the survival and death of activated T cells.
For full text by Zhan et al., see – https://www.frontiersin.org/articles/10.3389/fimmu.2017.01809/full
We thought we’d share some brief highlights of Australian epigenetics publications over the last three months:
From La Trobe University in Melbourne, Prof Whelan and team have published an insightful study that “reveals the complex dynamics and interactions of the transcriptome and epigenome during seed germination”. The study identifies the epigenomic and transcriptomic changes that Arabodpsis Thaliana seeds undergo as they transition from an embryo-like to vegetative seedling during germination. Further, by generating a transcription factor network model for germination, the authors identify known and novel regulatory factors that drive seed germination. The paper reveals extensive remodelling of the seed DNA methylome during this period of transformation. https://doi.org/10.1186/s13059-017-1302-3
In a joint effort by the laboratories of Prof Johnstone from the Peter MacCallum Cancer Centre and Dr Hawkins from The Walter and Eliza Hall Institute of Medical Research in Melbourne, Notch 1 signaling has been targeted as a novel therapeutic for T cell acute lymphoblastic leukemia (T-ALL). Using the notch driven T-ALL mouse model the authors investigate the therapeutic possibility of the histone deacetylase inhibitor (HDACi) panobinostat.
The study revealed that the drug was able to regulate T-ALL cellular proliferation, and that this was correlated with a loss of c-Myc expression in these cells. In vivo, Panobinostat treated mice had significantly increased survival compared to vehicle treated control leukemia mouse models.
A collaborative effort between Umeå University in Sweden, the University of Melbourne and Murdoch Children’s Research Institute in Melbourne published a population-based study on grandmaternal smoking during pregnancy and the risk of asthma in grandchildren. Lodge et. al. interrogated prospectively collected data from the national Swedish registries to reveal that “children aged 1-6 years had an increased asthma risk if their grandmothers had smoked during pregnancy.” The study further confirmed that maternal smoking did not modify this relationship.
In Nature Communications this month the group of Prof Susan Clark from the Garvan Institute of Medical Research in Sydney published on the role of the histone variant H2A.Z in enhancer activation in prostate cancer. Valdés-Mora et. al. reveal that an increased level of H2A.Z acetylation correlates with poor prognosis in prostate cancer samples. Using prostate cancer cell line models the study shows that androgen receptor associated enhancers require the incorporation of acetylated H2A.Z for activation and that H2A.Zac is mis-localized at active enhancers in cancer.
The study further demonstrates that acetylation of H2A.Z nucleosomes is associated with ectopic gene activation and epigenetic remodeling of cancer-specific regulatory elements. Collectively the study demonstrates a novel contribution of H2A.Zac in the activation of newly formed enhancers in prostate cancer.
From CSIRO in North Ryde, Sydney Dr Molloy and colleagues address the question of whether “…epigenetic marks present at birth may predict an individual’s future risk of obesity and type 2 diabetes”. For this van Dijk et. al. studied epigenetic marks from blood of newborn children and assessed whether they were associated with body mass index (BMI) and insulin sensitivity in these children later in childhood.In support of growing evidence on the role of epigenetics in programming of metabolic health, the study identified a number of DNA methylation regions at birth that were associated with obesity or insulin sensitivity measurements in childhood. The study also revealed associations between DNA methylation, maternal smoking and birth weight.