DNA provides the instructions to make us how we look and contributes to our life expectancy. Identical twins have exactly the same DNA, so why are slightly different in many ways? The answer is epigenetics.
Epigenetics is the name given to the science that studies the way in which cells package DNA so that only certain genes are used in one tissue, and other genes are used in other tissues. “Epi” means above, so epigenetics means “above” genetics. It provides instructions about how to package DNA to tell our cells what sort of cells to be, for example skin, brain, or heart cells.
All of the different cells in our body contain the same DNA (the same genes) and epigenetic factors determine which genes become either silenced if unneeded, or active if needed to make cells. Epigenetic factors are chemical tags on the DNA or on proteins called histones. These chemical tags attach to the DNA and are responsible for providing the DNA-packing signals inside cells. There are lots of different epigenetic factors and the number of new chemical tags discovered are increasing.
The chemical tags on the DNA are inherited during embryonic cell division, but they can change during normal developmental processes, such as puberty and pregnancy. Importantly, epigenetic factors or the chemical tags can also change due to environmental factors (diet, stress, toxins) and in certain diseases, such as cancer.
We now understand that epigenetic changes commonly take place when cancer develops and that they’re intimately involved in switching “off” critical cancer genes that should be “on” in normal cells and vice versa. This process results in a normal cell turning into a cancer cell.
Our laboratory is focused on understanding the epigenetic changes that occur in different types of cancer, including prostate cancer. Our current finding identifies a critical epigenetic chemical modification that occurs on a single histone when prostate cancer develops. This epigenetic change appears to lock and unlock genes that prevent and trigger cancer.
Epigenetic factors are ideal drug targets in cancer management, as they don’t change the DNA sequence but change how that sequence is packaged. The aim is to switch or reverse the epigenetic chemical modifications to potentially turn cancer cells back into normal cells.
There are currently drugs for the treatment of cancers, such as leukemias, that can reverse epigenetic changes approved by the US Food and Drug Administration (FDA). These are showing promising results with minimal side effects.
The next challenge is to develop epigenetic drugs that can treat patients with solid tumours, such as lung, breast or prostate cancer. To achieve these goals, we need to fully understand all the epigenetic changes that lead to cancer and identify new epigenetic drug targets.
We have demonstrated that, in prostate cancer, when one of the histones (a variant called H2A.Z) is chemically modified (or acetylated), cancer genes are activated and tumour suppressor genes are silenced. We propose that the enzyme that leads to chemical acetylation of H2A.Z could be an ideal drug target for prostate cancer.
A more detailed understanding of what is controlling the packaging of DNA inside our cells will not only get us closer to understanding what determines how we look and what contributes to our life expectancy, this knowledge will also give us new exciting approaches to treating diseases, such as cancer.
Susan Clark receives funding from NHMRC. She is affiliated with Garvan Institute of Medical Research
Fatima Valdes Mora receives funding from Prostate Cancer Foundation of Australia (2011-2013), Cure Cancer Australia and National Breast Cancer Foundation (2013-2017). She works for the Garvan Institute of Medical Research.