A consortium of researchers in the US and Australia has mapped the first complete human epigenome – work that could have major implications for diagnosing and treating diseases.
The human genome is made up of around 3bn DNA bases, and the sequence of the bases near to the genes often controls their activity. However, modifications of genes – by attaching methyl groups (methylation) to cytosine bases or variations in DNA packaging around the histone – can also affect expression of the genes. Such ‘epigenetic’ changes can be caused by external factors, such as diet and exposure to chemicals, and can play a crucial role in cancer and are known to be inheritable.
The researchers mapped, at single-base resolution, the methylome of human embryonic stem cells and lung fibroblasts. A comparison of the two cell types found that in fibroblasts the majority of cytosines, followed by a guanine, carried a methyl-group, as expected. But many of the methylations in the stem cells occurred at unusual sites (Nature doi:10.1038/nature08514).
Comparing the differences in methylation sites and, therefore, the genes influenced could help explain the pathways of various diseases, such as cancer.
‘The paper is a great example of how fast the field of epigenomics is progressing and of how embarrassingly little we know so far,’ says Bas Heijmans, of the molecular epidemiology department at Leiden University Medical Center in the Netherlands. ‘I expect a major push towards a better understanding of disease when follow-up work provides insights in the epigenetic differences between individuals – that is an epivariome map.’
According to the researchers from the University of Western Australia (UWA), the map will be a baseline for future studies, helping design tests to screen for epigenetic diseases, and the development of medicines that influence methylation and turn off cancer cells.
Defining the contribution of the epigenome to disease, however, is a quite formidable task, says Heijmans. ‘DNA methylation is only one aspect of epigenetic information… We know even less about the numerous different histone modifications, noncoding noncoding RNAs and their interplay,’ he points out.
This study, which is part of, and funded by, the National Institutes of Health (NIH) Roadmap Reference Epigenome Consortium, ‘represents a remarkable advance for human biology and medical science,’ says Harvey Millar, one of the researchers from the UWA. ‘It has been a truly international collaborative effort and we are very excited about the ground-breaking possibilities that may occur as a result.’
Some biotech companies are already focused on methylation-based diagnostics. For example, in October 2009, German molecular diagnostics firm Epigenomics launched the first in vitro diagnostic blood test for early detection of colorectal cancer. The test is based on detecting aberrant DNA methylation of the Septin9 gene from plasma samples.
Meanwhile, Joseph Ecker, one of the researchers from the Salk Institute in California, US, and his team are planning to examine how the methylome changes during normal development as well as examining a variety of disease states. ‘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,’ Ecker says.
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