Centre researchers part of US consortium that has mapped the human epigenome — the genome's new clothes

A major breakthrough study, published today in Nature, has provided a complete roadmap of the human epigenome and has major implications in the treatment of human diseases and for the development of stem-cell based regenerative medicine. An epigenome may be thought of as the clothes that dress a genome, controlling the way genes are packaged and expressed without actually altering the underlying DNA code. Epigenomes are flexible and can be changed by environmental factors such as diet, stress and chemical exposure, leading to changes in gene expression. These changes can be temporary or they can be more permanent, with some studies suggesting they can be passed down from generation to generation.

This research was conducted by an international consortium of The Salk Institute for Biological Studies; Ludwig Institute for Cancer Research and University of California San Diego; Morgridge Institute for Research, the Genome Centre for Wisconsin and The University of Wisconsin-Madison; and The University of Western Australia. It is part of, and funded by, the NIH Roadmap Reference Epigenome Consortium. The consortium including three researchers linked to the ARC Centre of Excellence in Plant Energy Biology and WA Government-funded State Centre of Excellence in Computational Systems Biology.

This is the first study to fully sequence the human epigenome at single-base resolution, and required re-sequencing the human genome more than thirty times to map the location of tens of millions of tiny biological markers known as cytosine methylation sites.

The paper also reveals a remarkable difference between normal human cells and stem cells in the type and pattern of methylation sites. The stem cells contain many methylations at unusual sites in the genome that must be actively propagated from one cell division to another. This finding could provide the key to understanding how stem cells can make many different cell types, while other human cells have defined roles that cannot be changed.

The lead researcher in this groundbreaking study was Dr. Ryan Lister, a former Centre PhD student from Professor Jim Whelan's laboratory, who has been based at the Salk Institute for Biological Studies in San Diego, California for several years.

UWA PhD student Mr Julian Tonti-Filippini, supervised by UWA Professor Harvey Millar, collaborated with Dr Lister to develop software tools for data handling, analysis and visualisation. This is the second collaboration between the three scientists, following on from a successful study that mapped the complete epigenome of the model plant Arabidopsis thaliana, published last year in the journal Cell.

Julian Tonti-Filippini makes the cover of Cell

Centre researchers Julian Tonti-Filippini and Harvey Millar collaborated with researchers from the JR Ecker Laboratory at the Salk Institute in San Diego to analyse DNA methylation and the mRNA and smRNA components of the transcriptome by new deep sequencing technologies. Julian's AnnoJ Web 2.0 genome browser, developed in the centre, was a key tool in the visualisation of this huge dataset. This groundbreaking research was published April 17th in Cell and the data can be viewed via AnnoJ at Salk.