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Toronto researchers discover how genes remember their function

Breakthrough may help understand schizophrenia and cancer

September 3, 2009 - Researchers at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, The Hospital for Sick Children (SickKids), and The University of Toronto have made a breakthrough in understanding how genes remember their past experience through Polycomb Response Elements (PRE), which are memory modules that switch genes on or off. This discovery may lead to insights into diseases such as schizophrenia and cancer.

In a study published in the September 4 issue of the journal Cell, Toronto scientists have identified the first mammalian PRE - previously it was only confirmed that PREs existed in fruit flies. Dr. Sabine Cordes, a Senior Investigator at the Lunenfeld, made the discovery together with her graduate student Angela Sing, by studying the Kreisler gene (MafB) – which is turned on in the hindbrain - in mouse models.

“We found that, as in flies, the PRE we discovered is located in a very precise region of the DNA, but is at quite a distance from the gene it is switching on or off,” explains Sing. “This came as a surprise, because in mammals, scientists only had been looking at the regions near the genes themselves. That is like looking for a light switch beside a light fixture when the switch is often far away.”

Dr. Cordes further explains that “now that we know what a vertebrate PRE looks like, we may be able to find more PREs and investigate what roles they play in mental illness or cancer. In our study, we concluded that this particular PRE sets the Kreisler gene’s genetic memory (turning it on or off). This gene has an impact in nervous system development and, possibly, cancers such as leukemia.”

The researchers also found that that the M33/Cbx2, a polycomb-type protein that may be associated with schizophrenia, controls the Kreisler PRE.  They found that reducing levels of M33 caused some of the Kreisler-expressing cells to forget what they were trying to become (their function). 

“This study is the first to identify a PRE memory module in mammals and provides the first glimpse into how they function” says Dr. James Ellis, a Senior Scientist at SickKids and Associate Professor of Molecular Genetics at The University of Toronto, who worked on the study with Dr. Howard Lipshitz, a Senior Scientist at SickKids and Professor and Chair of Molecular Genetics at The University of Toronto. “A particularly striking aspect of the research is that the Kreisler PRE worked when we put it into flies. So, these genetic memory modules were already present hundreds of millions of years ago in our last common ancestor. It’s this remarkable evolutionary conservation of fundamental processes that makes studying simple organisms like flies lead to major insights into human development and disease.”

This study received funding from the Canadian Institutes for Health Research.
 

About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital

The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre established in 1985, is one of the world's premier centres in biomedical research. Thirty-four principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit www.lunenfeld.ca.
 

About The Hospital for Sick Children

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

 
Media contacts

Melissa McDermott
Media and Communications Specialist
Mount Sinai Hospital
416-586-4800 ext. 8306
mmcdermott@mtsinai.on.ca

   

Suzanne Gold
Communications Specialist – Media Relations
The Hospital for Sick Children
416-813-7654, ext. 2059
suzanne.gold@sickkids.ca