Revealed at last: the epigenome

The first detailed map of the human epigenome has been published. The epigenome, sometimes described as the 'instruction manual' to the human genome, is a regulatory network of chemical switches that governs the activation of human genes, and is therefore ultimately responsible for how a person grows and develops. Scientists believe that this exciting work could lead to new treatments for a range of illnesses including mental conditions such as schizophrenia, and life-threatening diseases such as cancer. The map, released by American scientists in the journal Nature, is the first publication to come as a result of the $190m international project to map the epigenome, and will surely be the first of many to draw on the collaboration.

Almost 10 years ago the Human Genome Project revealed the raw building blocks of life, prompting predictions that science would quickly uncover the links between genes and diseases leading to a new age of medical understanding and more effective treatments. However, progress was slower than originally hoped as those links were far more complicated than previously imagined. It is still largely unknown how the 25,000 genes that are needed to make a healthy human combine and interact to promote normal development and produce healthy organs such as hearts and brains. Heart and brain cells, like nearly all of the 200 different types of human cell, contain the same genetic makeup as each other and scientists have long been aware that what makes one cell type different from another is which particular genes inside the cell are 'turned on' or 'switched off'. It is the epigenome that is responsible for this chemical switching process, and the new map should serve as a reference for future research, hopefully shedding light on the mechanisms involved and crucially, how they can go wrong.

It is also expected that the map will help us understand the intriguing results of many studies that suggest that how we live our lives today can have powerful repercussions on the behaviour and health of our grandchildren. For example, one such study indicated that a person's diet can affect how their grandchildren process food, and another found that the grandchildren of people who smoked as youngsters reached puberty early. These 'epigenetic' effects, where a heritable change in genome function occurs without a change in the underlying DNA sequence, are poorly understood at present.

'This knowledge will be extremely valuable for understanding diseases such as cancer and possibly even mental disorders. Right now we just don't know how the epigenome changes during the ageing process or how the epigenome is impacted by our environment or diet,' said lead author of the paper Joseph Ecker, of the Salk Institute in La Jolla, California, US, who produced his map of the human epigenome by examining embryonic stem cells and fetal fibroblasts from the lung. The hope is that by comparing the new map with the epigenomes of diseased cells, scientists will be able to work out how 'glitches' in the epigenome can lead to different diseases such as cancer. The research of Stefan Beck, a professor of medical genomics at University College London, UK, has been aiming to do precisely that, and he is particularly pleased about the publication of the epigenome map, commenting: 'We've been working for years to get the epigenome project off the ground and finally it's happening. It is absolutely exciting that the first fruits of the project are coming out.'

Some pharmaceutical companies have already developed treatments that reset epigenetic information in cancerous cells, reverting them back to their healthy state. Originally developed to treat lymphoma and lung cancer, these promising drugs are now being tested against a number of other types of cancer. However, it is unclear precisely how these drugs work, raising concerns with some. Ecker warned: 'Unless we know how these drugs affect the entire epigenome, we don't really understand their full mechanism of action.' With the publication of the epigenomic map we are taking the first steps towards understanding this mechanism, and developing drugs that reduce the risk of cancer, even potentially reversing it once it has become established.

Epigenetics will be addressed before a mixed lay and specialist audience for the first time on Wednesday 18 November 2009 at Does Genetics Matter? Help, the annual conference of the charity that publishes BioNews, the Progress Educational Trust (PET).