Professor Steven Jones is among B.C. scientists involved in a an international effort to map the entire human epigenome.

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Scientists work to map human epigenome

November 17, 2016
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B.C. scientists, including Steven Jones, a professor in SFU’s Department of Molecular Biology and Biochemistry, are playing a major role in an international effort to map the entire human epigenome—an initiative that may prove bigger than the Human Genome Project.

Researchers hope that by mapping the epigenome they will better understand how genes are switched on and off in different cell types in response to different environmental and chemical signals.

While much has been learned from studying the human genome, the effort has only partially uncovered the processes underlying cell determination. The identity of each cell type is largely defined by an instructive layer of molecular annotations on top of the genome – the epigenome – which acts as a blueprint unique to each cell type and developmental stage.

Unlike the genome, the epigenome changes as cells develop, and in response to changes in the environment. Defects in the factors that read, write and erase the epigenetic blueprint are involved in many diseases. The comprehensive analysis of the epigenomes of healthy and abnormal cells will facilitate both diagnosis and treatment.

A collection of 41 coordinated papers now published by scientists from across the International Human Epigenome Research Consortium (IHEC) sheds light on these processes and is advancing the field. Twenty-four manuscripts have now been published in Cell and Cell Press-associated journals and another 17 in other high-impact journals.

The Canadian contribution to the project is coordinated through the Canadian Epigenetics, Environment and Health Research Consortium Network (CEEHRC). Scientists from the BC Cancer Agency, UBC and SFU published three of the 41 papers, providing important insights into how epigenetic information is encoded during normal human development and how it becomes deregulated in disease.

Prof. Jones, who is also a professor at UBC and a director of the BC Cancer Agency’s Michael Smith Genome Sciences Centre, co-led the DNA sequencing work at the Epigenomic Data Coordination Centre and Centre for Epigenome Mapping Technologies.

What is the epigenome and why is it significant?

The epigenome is a layer of molecular modifications that sit on top of our DNA. Even though cells all have the same DNA—i.e. a genetic blueprint, the epigenome helps particular cell types to determine which parts it should be reading and using. The epigenome is therefore a major part of the mechanism that allows us to make cells of different kinds that can make different tissues and organs.

Why is this effort to "map" it underway?

It is a very basic research question. How do cells orchestrate the functioning of their genes? How are genes controlled?  What are the molecular mechanisms that contribute to turning a stem cell into a tissue or an organ? Only in the last five years or so have we had the technology to actually undertake this task. So it is very exciting for those researchers involved in cellular development.

How will mapping it inform what we know about cells and cell development?

It will help us to understand how the DNA in our genomes is being read by the cell, and which genes are being activated and which genes are being turned off. It also gives us further clues to which parts of our DNA are important in controlling the fates of cells.   

What impact could this have on our understanding/strategy around diseases like cancer?

We now know that many cancers manipulate the epigenome for their own purposes. Many genes that help establish the epigenome can be seen to be mutated in many different cancer types. So cancer is an obvious disease to benefit from this study. Already, anti-cancer drugs are being tested that specifically modulate the epigenetic processes.   

What were the key findings of your research published in Cancer Cell?

In the Cancer Cell paper we studied malignant rhabdoid tumours. These are rare but very lethal childhood cancers. In this study, for the first time, we were able to understand how the cancer state had changed the epigenome and how it was reading the DNA information differently from normal cells.

This has given us further insight into the molecular underpinnings of this disease and how these cells have become cancerous. We observed that between cases, although the cancers were all changing the epigenomes, they were not all changed the same way and patients showed different patterns. These differences will have implications for how we develop therapeutic approaches to these tumours, since we now would not expect them all to respond to the same therapy.