Ryan Lister


Australian Research Council Centre of Excellence in Plant Energy Biology, Harry Perkins Institute of Medical Research, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia


Covalent modifications of DNA and histones play critical roles in the regulation of gene expression, cell activity, development, and disease. DNA methylation is a critical layer of the vertebrate epigenome, however despite several decades of investigation, the precise roles of DNA methylation in the control of genome and cell activity are still not clearly understood. A major obstacle in deciphering the mechanistic roles of epigenomic modifications has been the inability to precisely control and change the modification states in the genome. However, genome editing technologies are now rapidly being repurposed to achieve editing of epigenomic modifications where desired in the genome, in order to elucidate the causal relationships between these modifications and genome regulation, and as artificial regulatory tools to control cell activity and identity. We employed a broadly active artificial epigenome modifying protein to achieve genome-wide manipulation of promoter DNA methylation, enabling comprehensive assessment of its effects upon transcription and histone modifications, and the stability of artificially induced methylation. Furthermore, we have developed new CRISPR-Cas9 based tools that enable highly specific addition or removal of DNA methylation at desired locations in the genome in a controlled fashion. In addition to optimizing the efficacy and specificity of these functional epigenomics tools, we have utilized them to explore the sensitivity of DNA binding proteins to DNA methylation state. Overall, recent developments in epigenome editing tools are providing new insights into the role of covalent genome modifications in regulating gene expression, and new platforms for the manipulation of cell activity and identity.