The emerging and largely overlooked field of epigenetics has cast doubt upon the traditional assumption that DNA sequences are the only factors in heredity.
Epigenetics studies heritable characteristics not encoded in the DNA itself. Instead, the field examines proteins called histones that decorate the DNA sequences. Typically thought to be mere genetic “packing material,” histones vary between individuals and may play a role in heredity itself.
“Histones have regulatory functions that control gene expression,” explained Dr. Peter Cheung, a U of T professor of medical biophysics at the Ontario Cancer Institute. Histones are like genetic bookmarks, flagging areas of DNA that are active or not.
The way that DNA is wound around histones determines whether or not a given gene is being expressed. When genetic material is in an open configuration, called euchromatin, the cell launches a repertoire of factors that turn genes on, making them express their genetic instructions. DNA in a closed configuration, or heterochromatin, can’t be accessed by the factors that switch genes on.
Histones are the first examples of epigenetic markers, heritable factors other than the DNA sequences themselves that affect gene expression, to be found in cells. The pattern of histones (and thus of open or closed DNA) varies between individuals.
Attaching a small molecule called a methyl group to a histone is one way to change histone patterns. Recently, scientists have discovered small numbers of variant histones residing in cells, which may also directly control which genes are active or not.
Cheung’s research interest is focused on the heritable, epigenetic role of histones. Studies in budding yeast, a lower eukaryote, have already confirmed a histone variant called Htz1 as an epigenetic marker of open chromatin. Cheung’s lab found an analogous molecule in human cells, the histone variant known as H2A.Z, which plays the same role in epigenetic regulation.
With this recent discovery, another piece of the puzzle of epigenetic regulation has been unraveled. But where does this level of control over DNA actually make a difference in an individual’s body?
Cheung’s group found that, as well as marking genes for expression, this histone variant is also found marking genes that are only expressed in specific conditions, like development.
During the embryonic development, cells begin to take on the different roles they will play in the body. It is crucial that genes be properly controlled and expressed at the right times. Factors controlling gene expression are crucial in keeping cells from taking a wrong turn. Properly functioning histones may be a means of controlling gene expression that helps prevent developmental defects.
Cheung’s research has contributed to our knowledge of gene regulation, and misregulation, such as in cancer cells, where gene expression machinery has gone haywire.
An understanding of gene expression control is very relevant to medical challenges like cancer. A hallmark of cancer cells in tumours is the inability to suppress a number of genes whose regulation has run amok.
“Tumour suppressors that are turned off, or [detrimental] oncogenes that are turned on will give you cancer. Misregulation of gene expression can lead to diseases like cancer,” said Cheung.
Knowing the components of gene regulation is essential, since it gives us a list of molecular candidates to target in battling cancer cells.
While most of the epigenetic research by Cheung and others deals with the molecular level of epigenetic regulation, the applications of this research to clinical treatments are fast approaching as the field matures at U of T and around the world.
