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Europe to map the human epigenome

DNA-modification studies get a multi-million euro boost.

The health-research division of the European Commission launches its largest-ever project next week with a €30-million (US$41-million) investment in understanding the human epigenome, the constellation of DNA modifications that shape how genes are expressed.

With the project, called BLUEPRINT, Europe intends to become a major player in the International Human Epigenome Consortium (IHEC), set up last year to help biologists understand how the epigenome influences health and disease.

All the cells that make up an individual originate from the same fertilized egg and share the same genome. But during development, cells acquire epigenetic changes — such as chemical modifications to DNA, and changes in the shape of its tightly coiled three-dimensional structure — that affect which genes will be active in which cells at a given time and which will be silent.

The epigenome then remains largely stable, so that a liver, for example, remains a liver throughout life. But small parts of the epigenome change constantly as the cell responds to environmental changes. The epigenome also changes in diseases, including cancer.

The importance of the epigenome in health and disease is becoming increasingly clear. But researchers studying it have faced a big hurdle: the lack of a reliable library of high-quality, quantitative reference epigenomes against which new data can be compared. Little is known, even, about how much the epigenome normally varies between individuals, or between the different cells in an individual.

Enter BLUEPRINT, which unites 41 institutions and more than 50 principal investigators across Europe who will contribute a further €10 million to the project. BLUEPRINT will provide at least 100 reference epigenomes toward the IHEC's goal of amassing 1,000 reference epigenomes by 2020.

BLUEPRINT has chosen to focus on the blood system. This should help move discoveries quickly into the clinic, as many diagnostic tests rely on blood samples. "Blood is also what gets stored in biobanks and used for genome analysis," says BLUEPRINT coordinator Henk Stunnenberg at the Nijmegen Center for Molecular Life Sciences in the Netherlands.

Beyond these conveniences, there was also a compelling biological rationale for the choice, he says. Unlike most tissues, blood cells are constantly renewed, so blood comprises a mix of cells at different stages of maturity. "Blood-cell epigenomes may reveal some general rules about how cells develop," Stunnenberg says.
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