Human epigenome mapped
Mapping the epigenome could help
researchers treat diseases and develop
stem-cell based regenerative medicine. 
Image: iStockphoto

A major breakthrough study, published 15 October in Nature, has provided a complete roadmap of the human epigenome and has major implications for the treatment of human diseases and 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.

Epigenome 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.

Such epigenetic changes have been shown to account for clear physical differences between otherwise genetically identical organisms.

Epigenetic changes are essential because correct timing of gene expression is needed for healthy physical development and for the prevention of genetically based diseases such as cancer.

Conducted by an international consortium, including three researchers linked to The University of Western Australia (UWA), this is the first study to fully sequence the human epigenome at single-base resolution, and required re-sequencing the human genome more than 30 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 UWA plant scientist now based at the Salk Institute for Biological Studies in San Diego, California.  UWA PhD student 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 a successful study that mapped the complete epigenome of the model plant Arabidopsis thaliana, published last year in the journal Cell.

“This study represents a remarkable advance for human biology and medical science,” Professor Millar said.  “It has been a truly international collaborative effort and we are very excited about the ground breaking possibilities that may occur as a result.

“Julian originally designed his software to better understand gene expression in plants but with some further development, it evolved into a set of tools for digitalising the human epigenetic code.”

Editor's Note: Original news release can be found here.