Written by Laura Glitsos Wednesday, 23 December 2009 00:00
THE mapping of the human epigenome, Time Magazine’s second top scientific discovery of 2009, was achieved with the invaluable research of University of Western Australia (UWA) scientists and may now hold the key for potential cancer therapies.
The team was led by former UWA scientist Dr Ryan Lister at the Salk Institute for Biological Studies and relied on UWA PhD student Julian Tonti-Filippini’s software program to visualise the massive amounts of research data.
The team mapped biological markers known as cytosine methylation sites, which sit on the genome itself.
“There’s so much data because the human genome is so big, there are 3 billion bases that make up our genome,” Mr Tonti-Filippini’s PhD supervisor, Professor Harvey Millar says.
“But we needed to analyse that 3 billion bases at total of 30 times because we’re using a technique where we chemically modify the DNA so that we can find these methylation sites … and as a particular site isn’t always methylated we need to survey each site many times so we can confidently say whether or not a modification has taken place.”
Understanding the role of the epigenome may explain how and why inherited and environmental influences alter gene expression, therefore providing clues to disease treatment, and to the future use of stem cell based regenerative medicine.
“One of the big things that make this study so important is the comparison between two human epigenomes; one was from fibroblasts which are basically normal human cells, the other was from stem cells that can differentiate to make many different types of human cells,” Prof Millar says.
“The pattern of methylation in the human stem cells was radically different.
“It was a complete surprise.
“And so there may be important information within this methylation pattern that explains why stem cells can differentiate to any cell.”
Prof Millar says the study makes it possible for people to investigate methylation patterns on a whole-genome level and therefore provide a pathway to future cancer therapies.
“People have known for a long time that you get hyper-methylation of certain DNA regions in cancer cells, which turns off the genes that normally stop cells from becoming cancerous.
“There are already drugs in development that target methylation. They try to change methylation patterns as a therapy, so cells gain control over themselves again.
“This research has shown there are many millions of methylation sites in the human genome and that you have to be careful with drugs that modify methylation because you can be doing a lot of different things at the same time.
“But this whole genome technology now provides people with a way of measuring, when they use these kinds of drugs, what they are doing and what the consequences are for the whole cell.”
The article, “Human DNA methylomes at base resolution show widespread epigenomic differences”, was published in Nature.
