What turns cells off or on?
McGill scientists discovery has implications for cancer, gene therapy and biotechnology.
A team of researchers from the Department of Pharmacology and Therapeutics at McGill University report today in the journal Nature the discovery of a new human gene that encodes a novel activity believed to be critical for reprogramming cells. The team led by Dr Moshe Szyf, an associate professor in the Department of Pharmacology and Therapeutics, included Dr Sanjoy Bhattacharya, a postdoctoral fellow in the laboratory, and doctoral candidates Shyam Ramchandani and Nadia Cervoni.
Organisms like humans and other vertebrates are composed of many organs; each organ is comprised of many kinds of tissues and each tissue is built from one or multiple cell types. Cells are the smallest unit of living organisms. Each cell carries within it all the genetic information required to build a complete organism. However, as they develop, different cell types silence or activate different parts of their genetic information so that each cell performs its specific function in the whole organism. "Obviously, one of the greatest and most important secrets of biology is how this is achieved," says Dr Szyf. "What locks a cell in a specific program and prevents it from reverting to earlier programs? Part of this process is controlled by enzymes that modify the DNA, DNA methyltransferases. To utilize the full potential of biotechnology one has to be able to unlock these genetic programs." Dr Szyf explains that early in development the pattern of modification inherited from the parents is erased so that the developing embryo can form new programs. "The enzymes responsible for this process have been a mystery for the last four decades. Most researchers have believed that such enzymes will have to perform an impossible chemical reaction and therefore reasoned that they do not exist," says Szyf. However, the discovery of the demethylase enzyme described by the McGill researchers has refuted this dogma and identifies a novel enzymatic reaction which has no documented precedence.
The researchers believe that understanding the new gene will allow them to control and reverse genetic programs. This could be critical for diverse fields of biotechnology such as cloning, stem cell therapy and gene therapy. Another important potential of the discovery is anticancer therapy. It has been known for two decades that cancer cells have inherent problems with the modification pattern of their genes. The gene discovered by the McGill team is highly expressed in many cancer cells and is believed to be a very important anticancer target. While additional work will be required to realize the full technological and therapeutic potential of the finding, the researchers hope that they have uncovered an extremely important lead.
